Dosage regimen for HIV capsid inhibitors

Abstract

The present disclosure relates to dosing regimens of HIV capsid inhibitors and methods for treating or preventing a human immunodeficiency virus (HIV) infection in a patient.

Description

Cross-reference to related applications

[0001] none Technical Field

[0002] This disclosure relates to dosing regimens for HIV capsid inhibitors and methods for treating or preventing human immunodeficiency virus (HIV) infection in patients. Background Technology

[0003] Viral capsid proteins (CAs) are essential for multiple stages of the HIV life cycle. During viral maturation following processing of the Gag polyprotein by the HIV protease, CAs self-assemble into the cone-shaped core of the mature HIV-1 virion. Containing this capsid core are viral RNA, nucleocapsid, reverse transcriptase, and integrase. Failure to generate a suitable core precludes infectivity. Furthermore, CAs contribute to several essential processes during the early stages of HIV replication, including playing a crucial role in regulating appropriate capsid core breakdown (uncoating) kinetics to ensure efficient and productive viral DNA synthesis via coupled reverse transcription, and facilitating the active transport of the pre-integration complex to the nuclear compartment to support viral DNA integration into the transcriptionally active locus. Defects in normal capsid function ultimately inhibit efficient nuclear uptake and integration of viral DNA into the host genome.

[0004] Human immunodeficiency virus (HIV) infection is a life-threatening and serious disease of great public health significance, affecting approximately 38,000,000 people worldwide, with about 26,000,000 receiving antiretroviral (ARV) therapy (UNAIDS. Global HIV & AIDS statistics, 2020 fact sheet). Advances in combination ARV therapies for HIV have led to significant improvements in morbidity and mortality by suppressing viral replication, maintaining immune function, and preventing disease progression to AIDS. Summary of the Invention

[0005] This disclosure provides a method for treating or preventing human immunodeficiency virus (HIV) infection in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a first time period; (ii) administering to the patient one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a second time period, wherein the second time period occurs after the first time period; and Wherein, if the patient misses a maintenance dose during the second time period and more than approximately 28 weeks have elapsed since the administration of the previous maintenance dose, the method further includes re-administering the starting dose of step (i) to the patient before restarting the administration of the one or more maintenance doses of step (ii).

[0006] This disclosure also provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first and second days, administer orally about 500 mg to about 700 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; (b) On day eight, oral administration of about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and (c) On day 15, administer subcutaneously a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of approximately 309 mg / mL; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, followed by the initial dose of steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further includes administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or When the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further includes, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof. as well as (ii) Administering one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a second time period, wherein the second time period occurs after the first time period.

[0007] This disclosure also provides a compound described herein or a pharmaceutically acceptable salt thereof for use in any of the methods described herein.

[0008] This disclosure also provides the use of the compounds described herein or pharmaceutically acceptable salts thereof for the preparation of medicaments for use in any of the methods described herein. Attached Figure Description

[0009] Figure 1 Simulated lenacapavir (LEN) concentration-time curves are shown for HIV-positive adults under phase 2 / 3 and simplified regimens. Arrows indicate LEN administration, occurring on days 1, 2, 8, and 15, and week 28 for the phase 2 / 3 regimen, and on days 1 and 2, and week 26 for the simplified regimen.

[0010] Figure 2 This shows a simulated LEN C in adults with HIV during weeks 24 to 32. 谷.

[0011] Figure 3 Simulated LEN concentration-time curves for the oral loading portion of the 2 / 3 dosing regimen are shown for individuals with HIV (PWH).

[0012] Figure 4 The simulated mean (90% CI) plasma lenapavir (LEN) concentrations are shown for different alternative dosing options after a missed day 2 oral dose for ≥6 days. Lines represent simulated means, and shaded areas represent the 90% confidence interval (CI) of the simulated means. The horizontal dashed line represents the IQ4 threshold at 15.5 ng / mL. Figures 5A to 5D Simulated LEN concentration-time curves for PWH administered in a 2 / 3 dosing regimen at the start of treatment are shown: Day 2 oral dose missed <6 days ( Figure 5A ); if the oral dose is missed for ≥6 days on day 2 ( Figure 5B ); Oral dose missed on day 8 (<6 days) Figure 5C ); and the oral dose missed for ≥6 days on day 8 ( Figure 5D The line represents the simulated mean. The shaded area represents the 90% confidence interval of the simulated mean. A subcutaneous (SC) dose of LEN 927 mg was simulated on day 15 in all scenarios.

[0013] Figures 6A to 6D Simulated LEN concentration-time curves for PWH with a 2 / 3 dosing regimen when restarting treatment at steady state are shown: Day 2 oral dose missed <6 days ( Figure 6A ); if the oral dose is missed for ≥6 days on day 2 ( Figure 6B ); Oral dose missed on day 8 (<6 days) Figure 6C ); and the oral dose missed for ≥6 days on day 8 ( Figure 6D The line represents the simulated mean. The shaded area represents the 90% confidence interval of the simulated mean. A LEN 927 mg SC dose was simulated on day 15 in all scenarios. Simulations of restarting treatment were performed at steady state 28 weeks after the last SC injection. Detailed Implementation

[0014] Lenapamil, a human immunodeficiency virus (HIV-1) capsid inhibitor, is indicated for the treatment of HIV-1 infection (e.g., in heavily treated adults with multidrug-resistant HIV-1 infection who have failed to respond to their current antiretroviral regimen due to resistance, intolerance, or safety concerns). The recommended dosage of lenapamil includes a starting dose (e.g., initial administration as described herein), followed by a maintenance dose (e.g., maintenance administration as described herein). During the maintenance dosing period, patients receiving lenapamil may miss the subcutaneous (SC) injection window (e.g., within 26 to 28 weeks of a previous lenapamil administration). If a patient misses or is expected to miss a SC injection, the patient may restart the starting dose before continuing the maintenance dosing schedule, as described herein.

[0015] Therefore, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a first time period; (ii) administering to the patient one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a second time period, wherein the second time period occurs after the first time period; and Wherein, if the patient misses a maintenance dose during the second time period and more than approximately 28 weeks have elapsed since the administration of the previous maintenance dose, the method further includes re-administering the starting dose of step (i) to the patient before restarting the administration of the one or more maintenance doses of step (ii).

[0016] In some embodiments, this disclosure further provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first and second days, administer orally about 500 mg to about 700 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; (b) On day eight, oral administration of about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and (c) On day 15, administer subcutaneously a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of approximately 309 mg / mL; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, followed by the initial dose of steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further includes administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or When the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further includes, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof. as well as (ii) Administering one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a second time period, wherein the second time period occurs after the first time period.

[0017] In some embodiments, if the patient misses the oral administration on the second day and the oral administration is missed for less than six days, the method further includes administering about 600 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, and then completing the initial dose of steps (b) and (c).

[0018] In some embodiments, if the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day.

[0019] In some embodiments, if the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day.

[0020] In some embodiments, if the patient misses the oral administration on day eight and the oral administration is missed for less than six days, the method further includes administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on day fifteen, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on day fifteen.

[0021] In some embodiments, if the patient misses the oral administration on day eight and the oral administration is missed for six or more days, the method further includes, on day fifteen, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on day fifteen, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof.

[0022] In any of the embodiments provided herein, the compound of formula Ia is a compound of formula Ib: Ib Or a pharmaceutically acceptable salt thereof. Compounds of formula Ib may also be called lenakapavir (or “LEN”) or N-((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazole-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropano[3,4]cyclopentano[1,2-c]pyrazol-1-yl)acetamide.

[0023] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered as a monotherapy (i.e., in the absence of an additional therapeutic agent). In some embodiments, a compound of formula Ia, or a pharmaceutically acceptable salt thereof, is administered in combination with one or more additional therapeutic agents, such as an anti-HIV agent.

[0024] In some embodiments, the method includes administering a compound of formula Ia or a pharmaceutically acceptable salt thereof. In some embodiments, the method includes administering a compound of formula Ib or a pharmaceutically acceptable salt thereof.

[0025] The synthesis and characterization of compounds of formulas Ia and Ib and their salts are described, for example, in US 20180051005 and US 20190300505, the contents of each of these patents are incorporated herein by reference in their entirety. Various forms and / or uses of compounds of formulas Ia and Ib are disclosed, for example, in US 20190083478, US 20190084963, US 20200038389A1 and US 20210188815, the contents of each of these patents are incorporated herein by reference in their entirety.

[0026] In some embodiments, the compound of formula Ia is applied as a sodium salt. In some embodiments, the compound of formula Ib is applied as a sodium salt.

[0027] Where no specific pharmaceutically acceptable salt and / or solvate of a compound of formula Ia or Ib is specifically mentioned, any dose (whether expressed in milligrams or weight percent) should be understood to refer to the amount of free acid (i.e., the compound of formula Ia or Ib). For example, a reference to "50 mg" of formula Ia or a pharmaceutically acceptable salt thereof refers to an amount of the compound of formula Ia or a pharmaceutically acceptable salt thereof, which provides the same amount of the compound of formula Ia as 50 mg of the free acid. In some embodiments, a dose of formula Ia mentioned as 50 mg contains approximately 51.1 mg of the sodium salt of formula Ia.

[0028] In some embodiments, the compounds provided herein (i.e., compounds of formula Ia or Ib) or their pharmaceutically acceptable salts are administered orally in the form of one or more tablets as described herein.

[0029] In some embodiments, the compounds provided herein (i.e., compounds of formula Ia or Ib) or pharmaceutically acceptable salts thereof are administered subcutaneously in the form of one or more solutions as described herein.

[0030] In some embodiments, the compounds provided herein (i.e., compounds of formula Ia or Ib) or pharmaceutically acceptable salts thereof are administered intramuscularly in the form of one or more solutions as described herein.

[0031] In some implementations, the first time period is approximately one day to approximately two weeks. In some implementations, the first time period is approximately one day to approximately fifteen days. In some implementations, the first time period is two days. In some implementations, the first time period is approximately two weeks. In some implementations, the first time period is fifteen days.

[0032] In some implementations, the starting dose provided herein comprises one or more oral administrations of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0033] In some embodiments, the starting dose provided herein comprises one or more intramuscular or subcutaneous administrations of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0034] In some implementations, the starting dose provided herein includes one or more subcutaneous administrations of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0035] In some implementations, the starting dose provided herein includes one or more intramuscular administrations of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0036] In some embodiments, the starting dose provided herein comprises a single or multiple oral administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and One or more intramuscular or subcutaneous administrations of compounds of formula Ia or Ib or their pharmaceutically acceptable salts.

[0037] In some embodiments, the starting dose provided herein comprises a single or multiple oral administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and One or more subcutaneous administrations of compounds of formula Ia or Ib or their pharmaceutically acceptable salts.

[0038] In some embodiments, the starting dose provided herein comprises a single or multiple oral administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and One or more intramuscular administrations of compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof.

[0039] In some implementations, the starting dose includes: On the first day, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of approximately 309 mg / mL, and approximately 500 mg to approximately 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered orally; and On the second day, administer orally approximately 500 mg to approximately 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0040] In some implementations, the first time period is two days, and the initial dose includes: On the first day, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of approximately 309 mg / mL, and approximately 500 mg to approximately 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered orally; and On the second day, administer orally approximately 500 mg to approximately 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0041] In some embodiments, on the first day, the subcutaneous administration is administered as two subcutaneous injections of approximately 309 mg / mL. In some embodiments, the subcutaneous administration comprises administering approximately 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof as two subcutaneous injections of approximately 309 mg / mL (e.g., two subcutaneous injections of 1.5 mL each, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof).

[0042] In some embodiments, oral administration is performed with one or two tablets (e.g., one or two tablets on the first day; one or two tablets on the second day; one or two tablets on the first day and one or two tablets on the second day; etc.). In some embodiments, oral administration is performed with two tablets.

[0043] In some embodiments, on the first day and the second day, oral administration is performed in the form of two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0044] In some embodiments, oral administration is carried out in the following manner: on the first day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and on the second day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0045] In some embodiments, oral administration is carried out in the following manner: on the first day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and on the second day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0046] In some embodiments, on the first day and the second day, oral administration is performed in the form of two tablets, each containing about 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0047] In some embodiments, on the first day and the second day, oral administration is performed in the form of two tablets, each containing about 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0048] In some embodiments, oral administration is carried out in the following manner: two tablets on the first day, each tablet containing about 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and two tablets on the second day, each tablet containing about 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0049] In some implementations, the starting dose includes: On the first day, 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was administered subcutaneously, and approximately 600 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was administered orally; and On the second day, approximately 600 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered orally.

[0050] In some implementations, the starting dose includes: On the first day, 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously, and two tablets are administered orally, each containing approximately 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and On the second day, two tablets are administered orally, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0051] In some implementations, the starting dose includes: On the first day and the second day, about 500 mg to about 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, administer orally approximately 200 mg to approximately 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and On day 15, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of approximately 309 mg / mL.

[0052] In some implementations, the first time period is fifteen days, and the starting dose includes: On the first day and the second day, about 500 mg to about 700 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, administer orally approximately 200 mg to approximately 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and On day 15, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of approximately 309 mg / mL.

[0053] In some embodiments, the oral administration on the first day and the second day is each administered in two tablets, each tablet containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0054] In some embodiments, the oral administration on the first and second days is administered in the following manner: on the first day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and on the second day, two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0055] In some embodiments, the oral administration on the eighth day is administered as a tablet containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the oral administration on the eighth day is administered as a tablet containing about 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0056] In some embodiments, the oral administration on the first and second days is administered in the form of two tablets, each tablet containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and The oral administration on the eighth day is administered in the form of a tablet containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0057] In some implementation schemes: The first day of oral administration is administered in two tablets, each containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. The second day's oral administration is administered in two tablets, each containing approximately 200 mg to approximately 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and The oral administration on the eighth day is administered in the form of a tablet containing about 200 mg to about 400 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0058] In some embodiments, the oral administration on the first and second days is administered in the form of two tablets, each tablet containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and The oral administration on the eighth day is administered in the form of a tablet containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0059] In some implementation schemes: The first day of oral administration is administered in two tablets, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. The second day's oral administration is administered in two tablets, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and The oral administration on the eighth day is administered in the form of a tablet containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0060] In some embodiments, on the fifteenth day, the subcutaneous administration is administered as two subcutaneous injections of approximately 309 mg / mL. In some embodiments, the subcutaneous administration comprises administering approximately 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof as two subcutaneous injections of approximately 309 mg / mL (e.g., two subcutaneous injections of 1.5 mL each, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof).

[0061] In some implementations, the starting dose includes: On the first day and the second day, approximately 600 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered orally; and On the fifteenth day, 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously.

[0062] In some implementations, the starting dose includes: On the first day, two tablets are administered orally, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. On the second day, two tablets were administered orally, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. On the eighth day, administer orally one tablet containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and On the fifteenth day, 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered subcutaneously.

[0063] In some implementations, the starting dose includes: On the first day, two tablets are administered orally, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. On the second day, two tablets were administered orally, each containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. On the eighth day, administer orally one tablet containing approximately 300 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof; and On the fifteenth day, two subcutaneous injections of 1.5 mL each were administered, each containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, the second time period begins approximately 24 to 28 weeks after the final administration of the initial dose described herein, for example, approximately 24, 25, 26, 27, or 28 weeks after the final administration of the initial dose described herein. In some embodiments, the second time period begins approximately 26 weeks after the final administration of the initial dose described herein.

[0065] In some embodiments, the second time period begins approximately 24 to 28 weeks after the final subcutaneous administration of the starting dose provided herein, for example, approximately 24, 25, 26, 27, or 28 weeks after the final subcutaneous administration of the starting dose described herein. In some embodiments, the second time period begins approximately 26 weeks after the final subcutaneous administration of the starting dose.

[0066] In some embodiments, the second time period begins approximately 24 to 28 weeks after the final oral administration of the starting dose provided herein, for example, approximately 24, 25, 26, 27, or 28 weeks after the final oral administration of the starting dose described herein. In some embodiments, the second time period begins approximately 26 weeks after the final oral administration of the starting dose.

[0067] In some implementations, each maintenance dose comprises subcutaneous administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 24 to 28 weeks.

[0068] In some implementations, each maintenance dose consists of two subcutaneous injections of approximately 309 mg / mL every 24 to 28 weeks.

[0069] In some implementations, each maintenance dose comprises a subcutaneous administration of 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof every 24 to 28 weeks (e.g., two subcutaneous injections of 1.5 mL each, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof).

[0070] In some embodiments, each maintenance dose comprises two subcutaneous injections of 1.5 mL each every 24 to 28 weeks, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, each maintenance dose comprises subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of approximately 309 mg / mL every 24 to 28 weeks.

[0071] In some implementations, each maintenance dose comprises two subcutaneous injections of approximately 309 mg / mL every 24 to 28 weeks, or approximately 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof administered subcutaneously.

[0072] In some implementations, each maintenance dose comprises subcutaneous administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof at a concentration of approximately 309 mg / mL every 26 weeks.

[0073] In some implementations, each maintenance dose consists of two subcutaneous injections of approximately 309 mg / mL every 26 weeks.

[0074] In some implementations, each maintenance dose comprises a subcutaneous administration of 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof every 26 weeks (e.g., two subcutaneous injections of 1.5 mL each, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof).

[0075] In some embodiments, each maintenance dose comprises two subcutaneous injections of 1.5 mL each every 26 weeks, each subcutaneous injection containing approximately 309 mg / mL of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, each maintenance dose comprises subcutaneous administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof at a concentration of approximately 309 mg / mL every 26 weeks.

[0076] In some implementations, each maintenance dose comprises approximately 927 mg of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, administered subcutaneously as two subcutaneous injections of approximately 309 mg / mL every 26 weeks.

[0077] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose to the patient, the initial dose comprising, on day one, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and oral administration of about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof; and On the second day, approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered orally. (ii) Administer one or more maintenance doses to the patient, each maintenance dose comprising subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks; Maintenance dose administration begins approximately 26 weeks after the final oral administration of the initial dose; and Wherein, if the patient misses a maintenance dose and more than approximately 28 weeks have elapsed since the previous maintenance dose was administered, the method further includes re-administering the initial dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

[0078] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose to the patient, the initial dose comprising, on the first and second days, an oral administration of about 600 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; On the eighth day, approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally; and On day 15, 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered subcutaneously. (ii) Administering a maintenance dose to the patient, the maintenance dose comprising subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks; Maintenance dose administration begins approximately 26 weeks after the final subcutaneous administration of the initial dose; and Wherein, if the patient misses a maintenance dose and more than approximately 28 weeks have elapsed since the previous maintenance dose was administered, the method further includes re-administering the initial dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

[0079] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first and second days, administer orally about 600 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; (b) On day eight, administer orally about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and (c) On day 15, administer 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, followed by the initial dose of steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further includes administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or When the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further includes, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof. as well as (ii) Administering one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a second time period, wherein the second time period occurs after the first time period.

[0080] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ib to the patient: Ib Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose to the patient, comprising, on day one, a subcutaneous administration of 927 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof, and an oral administration of approximately 600 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof; and On the second day, approximately 600 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof was administered orally. (ii) Administer one or more maintenance doses to the patient, each maintenance dose comprising a compound of formula Ib or a pharmaceutically acceptable salt thereof administered subcutaneously every 26 weeks at a concentration of about 309 mg / mL; Maintenance dose administration begins approximately 26 weeks after the final oral administration of the initial dose; and Wherein, if the patient misses a maintenance dose and more than approximately 28 weeks have elapsed since the previous maintenance dose was administered, the method further includes re-administering the initial dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

[0081] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ib to the patient: Ib Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administer an initial dose to the patient, which includes oral administration of about 600 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof on the first and second days; On day eight, approximately 300 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof was administered orally; and On day 15, administer 927 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof subcutaneously. (ii) Administering a maintenance dose to the patient, which comprises subcutaneous administration of a compound of formula Ib or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks; Maintenance dose administration begins approximately 26 weeks after the final subcutaneous administration of the initial dose; and Wherein, if the patient misses a maintenance dose and more than approximately 28 weeks have elapsed since the previous maintenance dose was administered, the method further includes re-administering the initial dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

[0082] In some embodiments, this disclosure provides a method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ib to the patient: Ib Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ib or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first and second days, administer orally about 600 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof; (b) On day eight, administer orally approximately 300 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof; and (c) On day 15, administer 927 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof subcutaneously; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of a compound of formula Ib or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, followed by the initial dose used in steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on day eight and the missed oral administration is less than six days later, the method further includes administering approximately 300 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof orally on day fifteen, and administering 927 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof subcutaneously on day fifteen; or If the patient misses the oral administration on day eight and misses the oral administration for six or more days, the method also includes, on day fifteen, oral administration of about 300 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof, and on day fifteen, subcutaneous administration of 927 mg of the compound of formula Ib or a pharmaceutically acceptable salt thereof. as well as (ii) administering to the patient one or more maintenance doses of a compound of formula Ib or a pharmaceutically acceptable salt thereof for a second time period, wherein the second time period occurs after the first time period.

[0083] In some embodiments, the compounds provided herein (e.g., compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof) are administered as a monotherapy (i.e., in the absence of an additional therapeutic agent). In some embodiments, the compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof are administered in combination with one or more additional therapeutic agents, such as anti-HIV agents.

[0084] In some implementations, the methods provided herein include preventing a patient from becoming infected with human immunodeficiency virus (HIV). In some implementations, the patient may be at risk of HIV infection or be at risk of such infection.

[0085] In some implementations, the patient is HIV negative. In some implementations, the HIV is HIV-1. In some implementations, the HIV is HIV-2. In some implementations, the HIV is both HIV-1 and HIV-2.

[0086] As used in this article, "HIV" or "human immunodeficiency virus" refers to HIV-1 and / or HIV-2.

[0087] The term "patient" refers to a person who requires therapeutic or preventative treatment for a viral infection, such as HIV infection.

[0088] As used herein, the term "prevention" refers to the administration of a compound, a pharmaceutically acceptable salt thereof, or a composition containing the compound or a pharmaceutically acceptable salt thereof, before or after exposure to the virus but before the onset of disease symptoms and / or before the virus is detected in the blood. The term also refers to the prevention of the onset of disease symptoms and / or the prevention of the virus from reaching detectable levels in the blood. This term includes pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and event-driven or "on-demand" prophylaxis. The term also refers to the prevention of perinatal HIV transmission from mother to infant by administering a compound, a pharmaceutically acceptable salt thereof, or a composition containing the compound or a pharmaceutically acceptable salt thereof to the mother before delivery and to the infant during the first few days of life. The term also refers to the prevention of HIV transmission via blood transfusion.

[0089] As used in this article, the term "C" tau "" refers to the drug concentration observed at the end of the dosing interval.

[0090] As used in this article, the term “exposure period” refers to the period during which a patient is exposed to HIV, ranging from a single event to multiple events over a long period.

[0091] In some embodiments, the methods disclosed herein may include event-driven administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof to a patient. As used herein, the terms “event-driven” or “event-driven administration” mean administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof in the following circumstances: (1) prior to an event that would expose the patient to HIV (or otherwise increase the patient’s risk of HIV infection) (e.g., 2 hours, 1 day, 2 days, 5 days, 7 days, 10 days, 14 days, 28 days (i.e., one month) or more prior to the event); and / or (2) during an event that would expose the patient to HIV (or otherwise increase the patient’s risk of HIV infection) (or more than one relapse event); and / or (3) after an event that would expose the patient to HIV (or otherwise increase the patient’s risk of HIV infection) (or after the final event in a series of relapse events). In some embodiments, event-driven administration is performed before the patient’s exposure to HIV. In some embodiments, event-driven administration is performed during the patient’s exposure to HIV. In some implementations, event-driven administration is performed after a patient has been exposed to HIV.

[0092] In some implementations, event-driven administration is performed before and during a patient's exposure to HIV.

[0093] In some implementations, event-driven application is performed both before and after a patient's exposure to HIV.

[0094] In some implementations, event-driven application is performed both during and after a patient's exposure to HIV.

[0095] In some embodiments, the methods disclosed herein involve administration, for example as pre-exposure prophylaxis (PrEP) and / or post-exposure prophylaxis (PEP), before and / or after an event that would expose a patient to HIV or otherwise increase the patient's risk of HIV infection. In some embodiments, the methods disclosed herein include pre-exposure prophylaxis (PrEP). In some embodiments, the methods disclosed herein include post-exposure prophylaxis (PEP). In some embodiments, the methods disclosed herein include both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).

[0096] In some implementations, the compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered to the patient prior to exposure to HIV.

[0097] In some implementations, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered to a patient during exposure to HIV.

[0098] In some implementations, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered to a patient after exposure to HIV.

[0099] In some implementations, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered to patients before and during their exposure to HIV.

[0100] In some implementations, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered to patients before and after exposure to HIV.

[0101] In some implementations, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered during and after a patient’s exposure to HIV.

[0102] In some implementations, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered to patients before, during, and after their exposure to HIV.

[0103] In some embodiments, the dose of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof administered during each time period (i.e., before, during, and after exposure) may be different, i.e., independently selected from any dose disclosed herein.

[0104] In some embodiments, for example, when administered as PrEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered 1 hour to 240 hours (i.e., within 10 days), 1 hour to 216 hours, 1 hour to 192 hours, 1 hour to 168 hours, 1 hour to 144 hours, 1 hour to 120 hours, 1 hour to 96 hours, 1 hour to 72 hours, 1 hour to 48 hours, 1 hour to 24 hours, or 1 hour to 12 hours before an event that would increase the patient's risk of HIV infection (e.g., before an HIV exposure event). In some embodiments, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered 14 days, 13 days, 12 days, 11 days, 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, or 1 day before an event that would increase the patient's risk of HIV infection (e.g., before an HIV exposure event). In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered 72 hours, 60 hours, 48 ​​hours, 24 hours, 12 hours, 9 hours, 6 hours, 4 hours, 3 hours, 2 hours, or 1 hour before an event that would increase the patient's risk of HIV infection (e.g., before an HIV exposure event). In some embodiments, when the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered before an event that would increase the patient's risk of HIV infection, it is administered daily before that event. In some embodiments, when the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered before an event that would increase the patient's risk of HIV infection, it is administered one to three times before that event. In some embodiments, when the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered before an event that would increase the patient's risk of HIV infection, it is administered once (i.e., once).

[0105] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately 14 days to approximately one day prior to the patient's exposure to HIV. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once daily, approximately 14 days prior to the patient's exposure to HIV.

[0106] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately 10 days to approximately 5 days prior to the patient's exposure to HIV. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 10 days to approximately 5 days prior to the patient's exposure to HIV.

[0107] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately 8 to 6 days prior to the patient's exposure to HIV. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 8 to 6 days prior to the patient's exposure to HIV.

[0108] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately 7 days prior to the patient's exposure to HIV. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 7 days prior to the patient's exposure to HIV.

[0109] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately 72 hours to approximately 1 hour prior to the patient's exposure to HIV. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 72 hours to approximately 1 hour prior to the patient's exposure to HIV.

[0110] In some implementations of the methods provided herein, pre-exposure prophylaxis (PrEP) includes continuous PrEP.

[0111] In some embodiments in which a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered prior to the patient’s exposure to HIV, the methods disclosed herein further include administering one or more additional doses of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof during and / or after the patient’s exposure to HIV.

[0112] In some embodiments, for example, when administered as part of a PrEP regimen or as part of a PEP regimen, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered during the period of the patient's exposure to HIV. In some embodiments in which a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered prior to HIV exposure, the compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered approximately every 7 days, approximately every 14 days, approximately every 21 days, approximately every 28 days, approximately every 35 days, approximately every 42 days, or approximately every 6 months, or approximately every 12 months during the period of HIV exposure (e.g., in a single dose). In some embodiments, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered approximately every 7 days, approximately every 14 days, approximately every 21 days, approximately every 28 days, approximately every 35 days, approximately every 42 days, approximately every 6 months, or approximately every 12 months during the period of the patient's exposure to HIV.

[0113] In some embodiments, the dose of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof administered before HIV exposure differs from the dose administered during and / or after HIV exposure. For example, in some embodiments, the dose of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is increased, for example, as a double dose, a triple dose, etc., compared to an earlier dose (e.g., a dose administered before HIV exposure). In some embodiments, the increased dose of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is a double dose. In some embodiments, the dose of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is reduced, for example, by half, compared to an earlier dose (e.g., a dose administered before HIV exposure).

[0114] In some implementations, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered in a single dose approximately 1 hour to approximately 10 days prior to the patient's exposure to HIV.

[0115] Other examples of PrEP and / or PEP can be found, for example, in the following literature: a clinical trial overview entitled “On Demand Antiretroviral Pre-exposure Prophylaxis for HIV Infection in Men Who Have Sex With Men” (Clinical Trial No. NCT01473472); a clinical trial overview entitled “Prevention of HIV in Île-de-France” (Clinical Trial No. NCT03113123); and Molina et al. N. Engl. J. Med. The full text of each of these documents (2015, 353:2237-2246) is incorporated into this paper by reference.

[0116] In some implementations, for example, when administered as part of a PrEP regimen or as part of a PEP regimen, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered 1 hour to 10 days, 1 hour to 7 days, 1 hour to 5 days, 1 to 72 hours, 1 to 48 hours, 1 to 36 hours, 1 to 24 hours, or 1 to 12 hours after an event that increases the patient’s risk of HIV infection (e.g., after HIV exposure).

[0117] In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered for 7, 14, 21, 28, 30, or 45 days after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered for 30 days after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered less than 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 12 hours, 18 hours, 24 hours, 36 hours, or 48 hours after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered for 1, 2, 3, 4, or 5 days after an event that increases the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered daily after an event that increases the patient's risk of HIV infection, it is administered once to three times after that event. In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once after an event that increases the patient's risk of HIV infection, it is administered once after that event.

[0118] In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof may be administered approximately once weekly, approximately once monthly, approximately once every two months, approximately once every three months, approximately once every four months, approximately once every five months, approximately once every six months, or approximately once every 12 months after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof may be administered approximately once weekly after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof may be administered approximately once monthly after an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 2 months after an event that increases the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 3 months after an event that increases the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 4 months after an event that increases the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 5 months after an event that increases the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 6 months following an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event). In some embodiments, for example, when administered as a PEP, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered approximately every 12 months following an event that would increase the patient's risk of HIV infection (e.g., after an HIV exposure event).

[0119] In some implementations, for example, when administered as a PEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof may be administered for one month, two months, three months, four months, five months, six months, or twelve months after an event that would increase the patient’s risk of HIV infection (e.g., after an HIV exposure event).

[0120] In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after an event that increases the risk of HIV infection in a patient, it is administered one to fifty times after that event. In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after an event that increases the risk of HIV infection in a patient, it is administered one to forty times after that event. In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after an event that increases the risk of HIV infection in a patient, it is administered one to thirty times after that event. In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after an event that increases the risk of HIV infection in a patient, it is administered one to twenty times after that event. In some embodiments, when a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after an event that increases the risk of HIV infection in a patient, it is administered one to fifteen times after that event. In some embodiments, when a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered after an event that would increase the patient's risk of HIV infection, it is administered one to ten times after that event. In some embodiments, when a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered after an event that would increase the patient's risk of HIV infection, it is administered one to five times after that event.

[0121] In some implementations, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered to a patient during exposure to HIV.

[0122] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered from about 1 hour to about 14 days after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once from about 1 hour to about 14 days after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once from about 1 hour to about 7 days after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once from about 1 hour to about 7 days after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered from about 1 hour to about 72 hours after a patient has been exposed to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 1 hour to approximately 72 hours after a patient's exposure to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 1 hour to approximately 24 hours after a patient's exposure to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 1 hour to approximately 24 hours after a patient's exposure to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 24 hours to approximately 72 hours after a patient's exposure to HIV (e.g., final exposure). In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered once approximately 24 hours to approximately 72 hours after a patient's exposure to HIV (e.g., final exposure).

[0123] In some implementations, for example, when administered as PrEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered before and after an event that would increase the patient’s risk of HIV infection. For example, in some embodiments, when administered as PrEP, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered 1 hour to 240 hours (i.e., within 10 days), 1 hour to 216 hours, 1 hour to 192 hours, 1 hour to 168 hours, 1 hour to 144 hours, 1 hour to 120 hours, 1 hour to 96 hours, 1 hour to 72 hours, 1 hour to 48 hours, 1 hour to 24 hours, or 1 hour to 12 hours before an event that would increase the patient's risk of HIV infection, and 1 hour to 240 hours (i.e., within 10 days), 1 hour to 216 hours, 1 hour to 192 hours, 1 hour to 168 hours, 1 hour to 144 hours, 1 hour to 120 hours, 1 hour to 96 hours, 1 hour to 72 hours, 1 hour to 48 hours, 1 hour to 36 hours, 1 hour to 24 hours, or 1 hour to 12 hours after such an event. For example, in some embodiments, one or more (e.g., one, two, or three) doses of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof are administered once a day to ten days (e.g., seven days) before an event that would increase the patient's risk of HIV infection and once a day to ten days after that event. In some embodiments, a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof is administered once a week, twice a week, three times a week, four times a week, or five times a week, or once or more (e.g., once, twice, or three times) starting 1 hour to 48 hours after an event that would increase the patient's risk of HIV infection.

[0124] This article also provides a method for reducing the risk of HIV infection in patients, which involves administering to patients a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0125] In some embodiments, methods for reducing the risk of HIV infection (e.g., HIV-1 and / or HIV-2) include administering to a patient a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0126] In some embodiments, the risk of HIV infection is reduced by at least about 40%, 50%, 60%, 70%, 80%, 90%, or 95% (compared to patients who have not been administered a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof according to any of the methods provided herein). In some embodiments, the risk of HIV infection is reduced by about 80%, 85%, or 90%. In some embodiments, the risk of HIV infection is reduced by at least about 75%. In some embodiments, the risk of HIV infection is reduced by at least about 80%. In some embodiments, the risk of HIV infection is reduced by at least about 85%. In some embodiments, the risk of HIV infection is reduced by at least about 90%.

[0127] In some implementations, the patient is a patient who has undergone intensive treatment. In some implementations, the methods provided herein include treating human immunodeficiency virus (HIV) infection in patients who have undergone intensive treatment.

[0128] In some embodiments, this disclosure relates to the use of compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof in the treatment of infections caused by HIV, including administering a therapeutically effective amount to a patient in need, wherein the patient is a patient with multidrug-resistant HIV infection who has undergone intensive treatment.

[0129] As used herein, “patients who have undergone intensive treatment” refers to HIV-infected patients who have limited treatment options due to multidrug-resistant HIV infection. For example, in some implementations, “patients who have undergone intensive treatment” refers to HIV patients who have developed resistance to at least one class of antiretroviral drugs selected from the group consisting of NRTI, NNRTI, PI, and INSTI.

[0130] In some implementations, "multidrug-resistant HIV infection" refers to resistance to at least one class of antiretroviral drugs selected from the group consisting of NRTI, NNRTI, PI, and INSTI. In some implementations, "multidrug-resistant HIV infection" refers to resistance to at least one class of antiretroviral drugs selected from the group consisting of NRTI, NNRTI, PI, and INSTI. In some implementations, "multidrug-resistant HIV infection" refers to resistance to at least one class of antiretroviral drugs selected from the group consisting of NRTI, NNRTI, PI, and INSTI. In some implementations, "multidrug-resistant HIV infection" refers to resistance to at least one class of antiretroviral drugs selected from the group consisting of NRTI, NNRTI, PI, and INSTI.

[0131] As used in this article, the term "NRTI" refers to nucleoside reverse transcriptase inhibitors or nucleotide reverse transcriptase inhibitors.

[0132] As used in this article, the term "NNRTI" refers to a non-nucleoside reverse transcriptase inhibitor or a non-nucleotide reverse transcriptase inhibitor.

[0133] As used in this article, the term "PI" refers to a protease inhibitor.

[0134] As used in this article, the term "INSTI" refers to an integrase strand transfer inhibitor.

[0135] As used in this article, when referring to HIV therapy or HIV treatment regimens, the terms "failed" or "not passed" mean a future outcome in HIV patients that excludes the use of the same agent or class of treatment. This could be due to insufficient initial viral response caused by pre-existing viral resistance, viral rebound due to emergency viral resistance, or patient inability to continue treatment due to intolerance or safety issues.

[0136] In the disclosed methods, the patient who has undergone intensive treatment is infected with multidrug-resistant HIV. In some embodiments, the patient who has undergone intensive treatment has multidrug-resistant HIV infection and is on an unapproved HIV treatment regimen. In some embodiments, the patient who has undergone intensive treatment has a viral load greater than approximately 1,000 copies of HIV RNA / mL.

[0137] In some embodiments, HIV infection is HIV-1 infection. In some embodiments, HIV-1 infection is characterized by resistance to antiretroviral drugs, such as resistance to one, two, three, four, or more classes of antiretroviral drugs (e.g., PI, NRTI, NNRTI, INSTI, etc.) via HIV-1 mutants. In some embodiments, HIV-1 infection is characterized by resistance to one or more classes of antiretroviral drugs via HIV-1 mutants. In some embodiments, HIV-1 infection is characterized by resistance to two or more classes of antiretroviral drugs via HIV-1 mutants. In some embodiments, HIV-1 infection is characterized by resistance to three or more antiretroviral drugs via HIV-1 mutants.

[0138] In some implementations, HIV-1 mutants are resistant to protease inhibitors (PI), nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTI), or integrase strand transfer inhibitors (INSTI).

[0139] In some implementations, HIV-1 infection is characterized by HIV-1 mutants, including but not limited to: (a) HIV-1 mutants resistant to PI (e.g., I50V, I84V / L90M, G48V / V82A / L90M, G48V / V82S, etc.); (b) HIV-1 mutants resistant to NRTI (e.g., K65R, M184V, 6TAM, etc.). (c) HIV-1 mutants resistant to NNRTI (e.g., K103N, Y181C, Y188L, L100I / K103N, K103N / Y181C, etc.); and / or (d) HIV-1 mutants resistant to INSTI (Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, R263K / M50I, etc.).

[0140] In some implementations, the HIV-1 mutant resistant to protease inhibitors is selected from I50V, I84V / L90M, G48V / V82A / L90M, and G48V / V82S.

[0141] In some implementations, HIV-1 mutants resistant to nucleoside or nucleotide reverse transcriptase inhibitors are selected from K65R, M184V, and 6TAM.

[0142] In some implementations, HIV-1 mutants resistant to non-nucleoside or non-nucleotide reverse transcriptase inhibitors are selected from K103N, Y181C, Y188L, L100I / K103N, and K103N / Y181C.

[0143] In some implementations, HIV-1 mutants resistant to integrase strand transfer inhibitors are selected from Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I.

[0144] In some embodiments, the patient is infected with HIV-1 resistant to at least one antiretroviral drug. In some embodiments, the patient is infected with multidrug-resistant HIV-1. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one, two, three, four, or more antiretroviral drugs. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one antiretroviral drug from each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs). In some embodiments, the different classes of antiretroviral drugs are selected from NRTIs, NNRTIs, and PIs. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NRTI and at least one NNRTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NRTI and at least one PI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NRTI and at least one INSTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NNRTI and at least one PI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NNRTI and at least one INSTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NRTI, at least one NNRTI, and at least one PI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 resistant to at least one NRTI, at least one NNRTI, and at least one INSTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one NRTI, at least one PI, and at least one INSTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one NNRTI, at least one PI, and at least one INSTI. In some embodiments, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one NRTI, at least one NNRTI, at least one PI, and at least one INSTI.

[0145] In some implementations, the patient is infected with multidrug-resistant HIV-1, which is resistant to at least one antiretroviral drug that is an NRTI. Examples of NRTIs include, but are not limited to, emtricitabine (FTC). ® ), Lamivudine (3TC; Epivir) ® Zidovudine (AZT); Retrovir ® ), and doxorinosine (ddI; Videox-EC) ® ), and dideoxyinosine (Videx) ® Tenofovir, tenofovir alafenamide (Vemlidy) ® Tenofovir disoproxil fumarate (Viread) ® Stavudine (d4T; Zerit) ® ), zacitabine (ddeoxycytidine, ddC; Hivid) ® ) and Ziagen ® ).

[0146] In some implementations, the patient is infected with multidrug-resistant HIV-1, which is resistant to at least one antiretroviral drug that is an NNRTI (neuro-internal respiratory tract inhibitor). Examples of NNRTIs include, but are not limited to, efavirenz (Sustiva). ® Intellectual ® Rilpivirine (Edurant) ® ), Viramune ® ) and dlavudine (Rescriptor ® ).

[0147] In some implementations, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug that acts as a PI (pipeline). Examples of PIs include, but are not limited to, agenerase inhibitors. ® Azanavir (Reyataz) ® Prezista ® ), fosanavir (Telzir) ® Lexiva ® Indinavir (Crixivan) ® ), Lopinavir (Kaletra) ® ), nelfinavir (Viracept) ® ), Norvir ® ), saquinavir (Invirase) ® ) and telanavir (Aptivus ® ).

[0148] In some implementations, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug that is an INSTI. Examples of INSTIs include, but are not limited to, retegvir (Isentress ® ), Etibravir (Vitekta) ® ), Tivicay ® ), Cabotewe and Bicagwe.

[0149] In some implementations, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug that acts as a gp41 fusion inhibitor. Examples of gp41 fusion inhibitors include, but are not limited to, epovitamide, emfuvirtide, BMS-986197, emfuvirtide biomodification, emfuvirtide biosimilar, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and sifvirtide.

[0150] In some implementations, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug that acts as a CCR5 co-receptor antagonist. Examples of CCR5 co-receptor antagonists include, but are not limited to, apravirone, vevicvirone, maravirone, cinevirovirone, PRO-140, adatabvir (RAP-101), nifevirone (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, and vMIP (Haimipu).

[0151] In some embodiments of the disclosed method, the patient has previously been treated with at least one antiretroviral drug prior to treatment with a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 3 months, such as at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, or at least 24 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 3 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 6 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 9 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 12 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 18 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 24 months. In some implementations, the patient has previously been treated with at least one antiretroviral drug for at least 30 months. In some implementations, the patient has previously been treated with at least one antiretroviral drug for at least 36 months.

[0152] In some embodiments of the disclosed method, the patient had not passed a previous HIV treatment regimen prior to treatment with a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments of the disclosed method, the patient had not passed an HIV treatment regimen at the start of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the previous HIV treatment regimen included administration of at least one antiretroviral drug. In some embodiments, the HIV-infected patient had relapsed after an initial response to a previous HIV treatment regimen (e.g., antiretroviral therapy). In some embodiments, prior to treatment with a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the patient had a viral load greater than about 50 copies of HIV RNA / mL after approximately 48 weeks of therapy (e.g., antiretroviral therapy).

[0153] In some embodiments, the prior treatment regimen includes administering at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the prior treatment regimen includes administering at least one antiretroviral drug from each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs). In some embodiments, the different classes of antiretroviral drugs are selected from NRTIs, NNRTIs, and PIs. In some embodiments, the prior treatment regimen includes administering at least one NRTI and at least one NNRTI. In some embodiments, the prior treatment regimen includes administering at least one NRTI and at least one PI. In some embodiments, the prior treatment regimen includes administering at least one NRTI and at least one INSTI. In some embodiments, the prior treatment regimen includes administering at least one NNRTI and at least one PI. In some embodiments, the prior treatment regimen includes administering at least one NNRTI and at least one INSTI. In some embodiments, the prior treatment regimen includes administration of at least one PI and at least one INSTI. In some embodiments, the prior treatment regimen includes administration of at least one NRTI, at least one NNRTI, and at least one PI. In some embodiments, the prior treatment regimen includes administration of at least one NRTI, at least one NNRTI, and at least one INSTI. In some embodiments, the prior treatment regimen includes administration of at least one NRTI, at least one PI, and at least one INSTI. In some embodiments, the prior treatment regimen includes administration of at least one NNRTI, at least one PI, and at least one INSTI.

[0154] In some implementations, the prior treatment regimen included the administration of at least one antiretroviral drug that acts as a gp41 fusion inhibitor.

[0155] In some implementations, the prior treatment regimen included the administration of at least one antiretroviral drug that acts as a CCR5 co-receptor antagonist.

[0156] In some implementations, prior treatment regimens include the administration of at least one antiretroviral drug as an NRTI. Examples of NRTIs include, but are not limited to, emtricitabine (FTC). ® ), Lamivudine (3TC; Epivir) ® Zidovudine (AZT); Retrovir ®), and doxorinosine (ddI; Videox-EC) ® ), and dideoxyinosine (Videx) ® Tenofovir, tenofovir alafenamide (Vemlidy) ® Tenofovir disoproxil fumarate (Viread) ® Stavudine (d4T; Zerit) ® ), zacitabine (ddeoxycytidine, ddC; Hivid) ® ) and Ziagen ® ).

[0157] In some implementations, prior treatment regimens include the administration of at least one antiretroviral drug that is an NNRTI. Examples of NNRTIs include, but are not limited to, efavirenz (Sustiva). ® Intellectual ® Rilpivirine (Edurant) ® ), Viramune ® ) and dlavudine (Rescriptor ® ).

[0158] In some implementations, the prior treatment regimen includes the administration of at least one antiretroviral drug as a PI. Examples of PIs include, but are not limited to, agenerase. ® Azanavir (Reyataz) ® Prezista ® ), fosanavir (Telzir) ® Lexiva ® Indinavir (Crixivan) ® ), Lopinavir (Kaletra) ® ), nelfinavir (Viracept) ® ), Norvir ® ), saquinavir (Invirase) ® ) and telanavir (Aptivus ® ).

[0159] In some implementations, prior treatment regimens include the administration of at least one antiretroviral drug as an INSTI. Examples of INSTIs include, but are not limited to, retegvir (Isentress ® ), Etibravir (Vitekta) ® ), Tivicay ® ), Cabotewe and Bicagwe.

[0160] In some implementations, the prior treatment regimen includes administration of at least one antiretroviral drug that is a gp41 fusion inhibitor. Examples of gp41 fusion inhibitors include, but are not limited to, epovitamide, emfuvirtide, BMS-986197, emfuvirtide biomodifiers, emfuvirtide biosimilars, HIV-1 fusion inhibitors (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and sifvirtide.

[0161] In some implementations, the prior treatment regimen included administration of at least one antiretroviral drug as a CCR5 co-receptor antagonist. Examples of CCR5 co-receptor antagonists include, but are not limited to, apravirone, vevicvirone, maravirone, cineviro, PRO-140, adatabvir (RAP-101), nifevirone (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, and vMIP (Haimipu).

[0162] In some embodiments of the disclosed method, HIV-infected patients who have undergone intensive treatment have a viral load of about 200 copies of HIV-1 RNA / mL (c / mL) to about 1,000,000 c / mL at the start of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, such as about 200 c / mL to about 500,000 c / mL, about 200 c / mL to about 250,000 c / mL, about 200 c / mL to about 100,000 c / mL, about 200 c / mL to about 50,000 c / mL, about 200 c / mL to about 25,000 c / mL, about 200 c / mL to about 10,000 c / mL, about 200 c / mL to about 5,000 c / mL, about 200 c / mL to about 3,000 c / mL, about 200 c / mL to about 2,000 c / mL, about 200 c / mL to about 2,000 c / mL, about 200 c / mL to about 5,000 c / mL, about 200 c / mL to about 3 ...5,000 c / mL, about 200 c / mL to about 5,000 c / mL, about 200 c / mL to about 5,000 c / mL, about 200 c / mL to about 5,000 c / mL mL to about 1,000 c / mL, about 200 c / mL to about 750 c / mL, about 200 c / mL to about 500 c / mL, about 500 c / mL to about 1,000,000 c / mL, about 500 c / mL to about 500,000 c / mL, about 500 c / mL to about 250,000 c / mL, about 500 c / mL to about 100,000 c / mL, about 500 c / mL to about 50,000 c / mL, about 500 c / mL to about 25,000 c / mL, about 500 c / mL to about 10,000 c / mL, about 500 c / mL to about 5,000 c / mL, about 500 c / mL Approximately 3,000 c / mL, approximately 500 c / mL to approximately 2,000 c / mL, approximately 500 c / mL to approximately 1,000 c / mL, approximately 500 c / mL to approximately 750 c / mL, approximately 750 c / mL to approximately 1,000,000 c / mL, approximately 750 c / mL to approximately 500,000 c / mL, approximately 750 c / mL to approximately 250,000 c / mL, approximately 750 c / mL to approximately 100,000 c / mL, approximately 750 c / mL to approximately 50,000 c / mL, approximately 750 c / mL to approximately 25,000 c / mL, approximately 750 c / mL to approximately 10,000 c / mL, approximately 750 c / mL From about 5,000 c / mL, from about 750 c / mL to about 3,000 c / mL, from about 750 c / mL to about 2,000 c / mL, from about 750 c / mL to about 1,000 c / mL, from about 1,000 c / mL to about 1,000,000 c / mL, from about 1,000 c / mL to about 500,000 c / mL, from about 1,000 c / mL to about 250,000 c / mL, from about 1,000 c / mL to about 100,000 c / mL, from about 1,000 c / mL to about 50,000 c / mL, from about 1,000 c / mL to about 25,000 c / mL, from about 1,000 c / mL to about 10,000 c / mL, about 1,000 c / mL to about 5,000 c / mL, about 1,000 c / mL to about 3,000 c / mL, about 1,000 c / mL to about 2,000 c / mL, about 2,000 c / mL to about 1,000,000 c / mL, about 2,000 c / mL to about 500,000 c / mL, about 2,000 c / mL to about 250,000 c / mL, about 2,000 c / mL to about 100,000 c / mL, about 2,000 c / mL to about 50,000 c / mL, about 2,000 c / mL to about 25,000 c / mL, about 2,000 c / mL to about 10,000 c / mL, about 2,000 c / mL approximately 5,000 c / mL, approximately 2,000 c / mL to approximately 3,000 c / mL, approximately 3,000 c / mL to approximately 1,000,000 c / mL, approximately 3,000 c / mL to approximately 500,000 c / mL, approximately 3,000 c / mL to approximately 250,000 c / mL, approximately 3,000 c / mL to approximately 100,000 c / mL, approximately 3,000 c / mL to approximately 50,000 c / mL, approximately 3,000 c / mL to approximately 25,000 c / mL, approximately 3,000 c / mL to approximately 10,000 c / mL, approximately 3,000 c / mL to approximately 5,000 c / mL, approximately 5,000 c / mL to approximately 1,000,000 c / mL Approximately 5,000 c / mL to approximately 500,000 c / mL, approximately 5,000 c / mL to approximately 250,000 c / mL, approximately 5,000 c / mL to approximately 100,000 c / mL, approximately 5,000 c / mL to approximately 50,000 c / mL, approximately 5,000 c / mL to approximately 25,000 c / mL, approximately 5,000 c / mL to approximately 10,000 c / mL, approximately 10,000 c / mL to approximately 1,000,000 c / mL, approximately 10,000 c / mL to approximately 500,000 c / mL, approximately 10,000 c / mL to approximately 250,000 c / mL, approximately 10,000 c / mL to approximately 100,000 c / mL, approximately 10,000 c / mL 00 c / mL to about 50,000 c / mL, about 10,000 c / mL to about 25,000 c / mL, about 25,000 c / mL to about 1,000,000 c / mL, about 25,000 c / mL to about 500,000 c / mL, about 25,000 c / mL to about 250,000 c / mL, about 25,000 c / mL to about 100,000 c / mL, about 25,000 c / mL to about 50,000 c / mL, about 50,000 c / mL to about 1,000,000 c / mL, about 50,000 c / mL to about 500,000 c / mL, about 50,000 c / mL to about 250,000 c / mL, about 50,Viral loads ranging from approximately 1,000 c / mL to approximately 100,000 c / mL, approximately 100,000 c / mL to approximately 1,000,000 c / mL, approximately 100,000 c / mL to approximately 500,000 c / mL, approximately 100,000 c / mL to approximately 250,000 c / mL, approximately 250,000 c / mL to approximately 1,000,000 c / mL, approximately 250,000 c / mL to approximately 500,000 c / mL, or approximately 500,000 c / mL to approximately 1,000,000 c / mL.

[0163] In some implementations, the patient has a viral load of more than about 200 copies of HIV-1 RNA / mL (c / mL) at the start of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, such as a viral load of more than about 500 c / mL, about 750 c / mL, about 1,000 c / mL, about 2,000 c / mL, about 3,000 c / mL, about 5,000 c / mL, about 10,000 c / mL, about 25,000 c / mL, about 50,000 c / mL, about 100,000 c / mL, about 250,000 c / mL, about 500,000 c / mL, or more than about 1,000,000 c / mL at the start of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has a viral load greater than about 200 c / mL when starting administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has a viral load greater than about 500 c / mL when starting administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has a viral load greater than about 750 c / mL when starting administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has a viral load greater than about 1,000 c / mL when starting administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the patient has a viral load greater than about 2,000 c / mL when starting administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof.

[0164] In some embodiments of the disclosed method, administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, results in a reduction in viral load in the patient. In some embodiments, the viral load is reduced by approximately 0.5 log after a certain period of time following administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof. 10 To approximately 2.5 log 10For example, the viral load after a certain amount of time following administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof decreased by approximately 0.5 log compared to the viral load at the start of administration of the compound or a pharmaceutically acceptable salt thereof. 10 Approximately 1 log 10 Approximately 1.5 log 10 Approximately 2 logs 10 or approximately 2.5 log 10 In some implementations, the viral load after approximately 24 weeks of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is reduced by approximately 0.5 log compared to the viral load at the start of administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof. 10 In some implementations, the viral load after approximately 24 weeks of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is reduced by approximately 1 log compared to the viral load at the start of administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof. 10 In some implementations, the viral load after approximately 24 weeks of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is reduced by approximately 1.5 log compared to the viral load at the start of administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof. 10 In some implementations, the viral load after approximately 2 log10 weeks of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof was reduced compared to the viral load at the start of administration of the compound or a pharmaceutically acceptable salt thereof. 10 In some implementations, the viral load after approximately 24 weeks of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is reduced by approximately 2.5 log compared to the viral load at the start of administration of the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof. 10 .

[0165] In some embodiments of the disclosed method, after a certain period of time following administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 200 c / mL or less, such as about 175 c / mL or less, about 150 c / mL or less, about 125 c / mL or less, about 100 c / mL or less, about 75 c / mL or less, or about 50 c / mL or less. In some embodiments, after about 24 weeks of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 200 c / mL or less. In some embodiments, after about 24 weeks of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 200 c / mL or less. In some embodiments, after about 24 weeks of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 100 c / mL or less. In some implementations, after approximately 24 weeks of administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, the viral load in the patient is approximately 50 c / mL or less.

[0166] In some embodiments of the disclosed method, patients who have undergone intensive treatment are simultaneously treated with at least one additional antiretroviral agent. In some embodiments, the antiretroviral agent is selected from NRTI, NNRTI, PI, INSTI, gp41 fusion inhibitors, and CCR5 co-receptor antagonists.

[0167] In some implementations, the patient is treated simultaneously with at least one NRTI. Examples of NRTIs include, but are not limited to, emtricitabine (FTC). ® ), Lamivudine (3TC; Epivir) ® Zidovudine (AZT); Retrovir ® ), and doxorinosine (ddI; Videox-EC) ® ), and dideoxyinosine (Videx) ® Tenofovir, tenofovir alafenamide (Vemlidy) ® Tenofovir disoproxil fumarate (Viread) ® Stavudine (d4T; Zerit) ® ), zacitabine (ddeoxycytidine, ddC; Hivid) ® ) and Ziagen ® ).

[0168] In some implementations, the patient is treated simultaneously with at least one NNRTI. Examples of NNRTIs include, but are not limited to, efavirenz (Sustiva). ® Intellectual® Rilpivirine (Edurant) ® ), Viramune ® ) and dlavudine (Rescriptor ® ).

[0169] In some implementations, the patient is treated simultaneously with at least one PI. Examples of PIs include, but are not limited to, agenerase. ® Azanavir (Reyataz) ® Prezista ® ), fosanavir (Telzir) ® Lexiva ® Indinavir (Crixivan) ® ), Lopinavir (Kaletra) ® ), nelfinavir (Viracept) ® ), Norvir ® ), saquinavir (Invirase) ® ) and telanavir (Aptivus ® ).

[0170] In some implementations, the patient is treated simultaneously with at least one INSTI. Examples of INSTIs include, but are not limited to, retegvir (Isentress ® ), Etibravir (Vitekta) ® ), Tivicay ® ), Cabotewe and Bicagwe.

[0171] In some implementations, patients are treated simultaneously with at least one gp41 fusion inhibitor. Examples of gp41 fusion inhibitors include, but are not limited to, epovitamide, emfuvirtide, BMS-986197, emfuvirtide biomodifiers, emfuvirtide biosimilars, HIV-1 fusion inhibitors (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and sifvirtide.

[0172] In some implementations, patients are treated concurrently with at least one CCR5 co-receptor antagonist. Examples of CCR5 co-receptor antagonists include, but are not limited to, apravirone, vevicvirone, maravirone, cinevirovirone, PRO-140, adatabvir (RAP-101), nifevirone (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, and vMIP (Haimipu).

[0173] This disclosure also provides a method for treating HIV-1 infection in a multidrug-resistant HIV-1 patient who has undergone intensive treatment, the method comprising administering to a patient who has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug and has failed to complete that treatment regimen a therapeutically effective amount of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the HIV treatment regimen comprises administration of at least one antiretroviral drug, such as those described herein. In some embodiments of the method, administration of a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof results in a reduction in the HIV viral load in the patient.

[0174] A method for treating HIV-1 infection in a patient with multidrug-resistant HIV-1 who has undergone intensive treatment is also disclosed. The method comprises administering a therapeutically effective amount of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, to a patient who has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug and has failed to complete that regimen. The multidrug-resistant HIV-1 is resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from NRTI, NNRTI, PI, and INSTI. In some embodiments, the patient has a viral load greater than about 200 c / mL at the start of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, and administration of the compound results in a reduction of the HIV viral load in the patient.

[0175] In some embodiments, a method for treating HIV-1 infection in a patient with multidrug-resistant HIV-1 who has undergone intensive treatment is disclosed. The method comprises administering a therapeutically effective amount of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, to a patient who has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug and has failed to complete that regimen. The multidrug-resistant HIV-1 is resistant to at least one antiretroviral drug from each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from NRTI, NNRTI, PI, and INSTI. In some embodiments, the patient has a viral load greater than about 200 c / mL at the start of administration of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, and administration of the compound results in a reduction of the HIV viral load in the patient.

[0176] Salts and Compositions The method of this invention includes administering a salt of a compound of formula Ia or Ib, such as a pharmaceutically acceptable salt. A salt generally refers to a derivative of the disclosed compound, wherein the parent compound is modified by converting an existing acid or base moiety into its salt form. A pharmaceutically acceptable salt is one that, within reasonable medical judgment, is suitable for contact with human and animal tissues without excessive toxicity, irritation, allergic response, or other problems or complications, and is commensurate with a reasonable benefit / risk ratio. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali metal or organic salts of acidic residues such as carboxylic acids; and so on. Pharmaceutically acceptable salts of this disclosure include, for example, conventional non-toxic salts of parent compounds formed from non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of this disclosure can be synthesized by conventional chemical methods from parent compounds containing a basic or acidic moiety. Typically, such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of a suitable base or acid. A list of suitable salts is available in […]. Remington's Pharmaceutical Sciences 17th edition, Mack Publishing Company, Easton, Pa., 1985, page 1418 and Journal of Pharmaceutical Science The full text of each of these documents is incorporated herein by reference in , 66, 2 (1977). In some implementations, the salt is a sodium salt.

[0177] Compounds of formula Ia or Ib or salts thereof may be present in a composition (such as a pharmaceutical composition or formulation) wherein the composition comprises at least one compound other than compounds of formula Ia or Ib or salts thereof.

[0178] In some embodiments, the composition comprises a compound of formula Ia or Ib or a salt thereof and one or more additional compounds (e.g., one or more additional therapeutic compounds) or salts thereof. In some embodiments, the composition comprises a compound of formula Ia or Ib or a salt thereof; bicagvir or a salt thereof; and one or more additional compounds (e.g., one or more additional therapeutic compounds, such as tenofovir alafenamide or a pharmaceutically acceptable salt thereof) or salts thereof.

[0179] The composition may include a compound of formula Ia or Ib or a salt thereof and a mixture of one or more solvents, substrates, carriers, etc. In some embodiments, the composition contains more than about 25% by weight (e.g., more than about 25% by weight, more than about 50% by weight, more than about 75% by weight, more than about 80% by weight, more than about 90% by weight, or more than about 95% by weight) of a compound of formula Ia or Ib or a salt thereof.

[0180] This disclosure further includes pharmaceutical compositions comprising compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof, and at least one pharmaceutically acceptable carrier. As used herein, "pharmaceutically acceptable carrier" means any adjuvant, carrier, excipient, flow aid, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that has been approved by the U.S. Food and Drug Administration for acceptable use in humans or domestic animals.

[0181] The administration of compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, can be performed via any approved pharmaceutical administration modality used for similar utilities. The pharmaceutical compositions of this disclosure can be prepared by combining compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, with a suitable pharmaceutically acceptable carrier, and in specific embodiments, are formulated as preparations in solid, semi-solid, liquid, or gaseous form, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalers, gels, microspheres, and aerosols. Exemplary routes of administration of such pharmaceutical compositions include, but are not limited to, oral, topical, transdermal, inhalation, parenteral, sublingual, buccal, rectal, vaginal, and intranasal administration. In some embodiments, the pharmaceutical compositions of this disclosure are tablets. In some embodiments, the pharmaceutical compositions of this disclosure are injections (e.g., intramuscular (IM) or intraperitoneal (IP)). The pharmaceutical compositions of this disclosure are formulated to allow the active ingredient contained therein to be bioavailable when the composition is administered to a patient. The composition to be administered to a patient will be in the form of one or more dose units, wherein, for example, a tablet may be a single dose unit, and a container for a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, in the form of an aerosol may contain multiple dose units. Practical methods for preparing such dosage forms are known or will be obvious to those skilled in the art; see, for example, Remington: The Science and Practice of Pharmacy, 20th edition (Philadelphia College of Pharmacy and Science, 2000). In any event, the composition to be administered will contain a therapeutically effective amount of a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, for the purpose of preventing HIV infection or reducing the risk of HIV infection, as described herein.

[0182] In some embodiments, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered parenterally. Parenteral administration includes, but is not limited to, intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, intracranial, transdermal, and vaginal administration. Parenteral administration may be, for example, in the form of a single bolus dose or via a continuous infusion pump. In some embodiments, compounds of formula Ia or Ib, or pharmaceutically acceptable salts thereof, are administered to a patient via a medical device. Exemplary medical devices include, but are not limited to, patches (e.g., transdermal patches), implantable devices (e.g., implantable devices for metering or sustained release of an active agent; subcutaneous devices), syringes, contraceptive devices (e.g., vaginal rings, intrauterine contraceptive devices), etc.

[0183] In some implementations, formulations suitable for parenteral administration (e.g., intramuscular (IM) and subcutaneous (SC) administration) will contain one or more excipients. The excipients should be compatible with the other components of the formulation and physiologically harmless to the recipient. Examples of suitable excipients are well known to those skilled in the art of parenteral formulations and can be found, for example, in the Handbook of Pharmaceutical Excipients (edited by Rowe, Sheskey, and Quinn), 6th edition, 2009.

[0184] Examples of solubilizing excipients in parenteral formulations (e.g., SC or IM formulations) include, but are not limited to, polysorbates (such as polysorbate 20 or 80) and poloxamer (such as poloxamer 338, 188, or 207). In some embodiments, this document discloses parenteral administration (e.g., SC or IM formulations) comprising a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, and poloxamer. In some embodiments, the poloxamer is poloxamer 338. In some embodiments, the poloxamer is poloxamer 188. In some embodiments, the amount of poloxamer in the parenteral administration disclosed herein is less than about 10%, such as less than about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, about 1%, or about 0.5%. In some embodiments, the amount of poloxamer in the parenteral administration disclosed herein is less than about 5%, such as less than about 3%, about 2%, about 1%, or about 0.5%.

[0185] In some embodiments, the excipients include N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide, polyethylene glycol, and / or tetraethylene glycol / tetrahydrofuran polyethylene glycol ether.

[0186] Generally, poloxamer is a synthetic nonionic triblock copolymer of a linear copolymer having a central hydrophobic chain of polyoxypropylene adjacent to two hydrophilic polyoxypropylene segments, wherein the polyoxypropylene to the two hydrophilic polyoxypropylene segments are in a weight ratio of 4:2:4 in some cases. Therefore, in some embodiments, the compositions disclosed herein comprise compounds of formula Ia or Ib or pharmaceutically acceptable salts thereof, and block copolymers consisting of one polyoxypropylene segment and two hydrophilic polyoxypropylene segments. In some embodiments, the ratio of the polyoxypropylene segment to the two hydrophilic polyoxypropylene segments is 4:2:4 (hydrophilic polyoxypropylene:polyoxypropylene:hydrophilic polyoxypropylene). Poloxamer is generally understood to have the following structure: , Where a and b are integers. For example, a is between about 2 and about 130, and b is between about 15 and about 67. For example, poloxamer 188 is understood to have a molecular weight of about 7680 Daltons to about 9510 Daltons (where a is about 80 and b is about 27) (see, for example, International Journal of PharmTech Research, Vol. 1, No. 2, pp. 299–303, April–June 2009). In some cases, the average molecular weight of poloxamer 188 is about 8400 Daltons. The molecular weight range of poloxamer 338 is from about 12700 Da to about 17400 Da (where a is about 141 and b is about 44).

[0187] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein do not contain poloxamer. In some embodiments, the pharmaceutical compositions disclosed herein do not contain poloxamer 188. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions that do not contain poloxamer. In some embodiments, the pharmaceutical compositions disclosed herein are solutions that do not contain poloxamer 188.

[0188] Examples of excipients in parenteral formulations (e.g., SC or IM formulations) include polyethylene glycol. Typically, polyethylene glycol (PEG) has the general formula H-(O-CH2-CH2). n -OH polyethers. In some embodiments, PEG can be "terminated" with alkyl groups. In those embodiments, the terminated PEG has the formula alkyl-(O-CH2-CH2). n -O-alkyl (e.g., CH3-(O-CH2-CH2)) n -OCH3). The pharmaceutical compositions disclosed herein may include PEG with an average molecular weight of about 100 to about 1000. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 100 to about 800. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 200 to about 600. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 400. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 300. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 200. In some embodiments of the pharmaceutical composition, PEGs of different molecular weights may be combined to obtain one or more desired properties (e.g., viscosity). Specific examples of PEG include, but are not limited to, PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, and PEG 600. For example, PEG 100 refers to polyethylene glycol with an average molecular weight of about 100.

[0189] The pharmaceutical compositions disclosed herein may be in the form of sterile injectable preparations, such as solutions or sterile injectable aqueous or oily suspensions. These suspensions may be formulated using suitable dispersants or wetting agents and suspending agents already mentioned herein, according to known techniques. Sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic, parenteral-acceptable diluents or solvents (such as solutions in 1,3-butanediol), or prepared as lyophilized powders. Acceptable solvents and media that may be used are water, Ringer's solution, and isotonic sodium chloride solution. Furthermore, sterile, non-volatile oils are generally used as solvents or suspension media. For this purpose, any mild, non-volatile oil may be used, including synthetic monoglycerides or diglycerides. Additionally, fatty acids such as oleic acid may also be used in the preparation of injectable formulations.

[0190] In some embodiments, the sterile injectable preparations disclosed herein can also be sterile injectable solutions or suspensions (such as solutions in 1,3-butanediol) prepared from reconstituted lyophilized powders in non-toxic, parenteral-acceptable diluents or solvents. Acceptable solvents and solvents that can be used are water, Ringer's solution, and isotonic sodium chloride solution. Furthermore, sterile non-volatile oils are generally used as solvents or suspension media. For this purpose, any mild non-volatile oil can be used, including synthetic monoglycerides or diglycerides. Additionally, fatty acids such as oleic acid can also be used in the preparation of injectables. Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injectable solutions that may contain antioxidants, buffers, antibacterial agents, and solutes to make the formulation isotonic with the intended recipient's blood; and aqueous and non-aqueous sterile suspensions that may include suspending agents and thickeners. In some embodiments, the suspension is a microsuspension. In some embodiments, the suspension is a nanosuspension.

[0191] In some embodiments, the pharmaceutical compositions of this disclosure may be in the form of a solution formulation. In some embodiments, the solution comprises N-methyl-2-pyrrolidone (NMP), polyethylene glycol (PEG), water, and / or tetrahydrofuran polyethylene glycol ether. In some embodiments, the solution comprises PEG 200, ethanol, and water. In some embodiments, the solution comprises PEG 300 and water. In some embodiments, the amount of water in the solution comprising PEG 300 and water is about 25 w / w%, about 23 w / w%, about 20 w / w%, about 17 w / w%, about 15 w / w%, about 10 w / w%, about 9 w / w%, about 8 w / w%, or about 5 w / w. In some embodiments, the amount of water in the solution containing PEG 300 and water is about 90 w / w, about 85 w / w, about 80 w / w, about 75 w / w, about 70 w / w, about 65 w / w, about 60 w / w, about 55 w / w, about 50 w / w, or about 45 w / w. In some embodiments, the solution containing PEG 300 and water contains about 85 w / w of PEG 300 and about 15 w / w of water. In some embodiments, the solution contains PEG 300 and water. In some embodiments, the solution containing PEG 300 and water also contains an inorganic base. In some embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In some embodiments, the amount of sodium hydroxide or sodium ethoxide is about 3 w / w, about 2 w / w, about 1 w / w, or about 0.5 w / w.

[0192] In some implementations, the compound of formula Ia or Ib or its pharmaceutically acceptable salt is administered orally, subcutaneously, intramuscularly, or intravenously.

[0193] In some implementations, the compound of formula Ia or Ib or its pharmaceutically acceptable salt is administered subcutaneously.

[0194] In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 10 mg / mL to about 600 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 10 mg / mL to about 500 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 50 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 100 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 125 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 150 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 175 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 300 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 309 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 400 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 500 mg / mL. In some embodiments, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered subcutaneously at a concentration of about 600 mg / mL.

[0195] In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 10 mg / mL to about 600 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 10 mg / mL to about 500 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 200 mg / mL to about 500 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 100 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 200 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 300 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 400 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 500 mg / mL. In some embodiments, the compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered intramuscularly at a concentration of about 600 mg / mL.

[0196] In some embodiments of the methods provided herein, compounds of formula Ia or Ib are administered to a patient as an injectable solution (e.g., for subcutaneous or intramuscular administration).

[0197] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ia, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a sodium salt of a compound of formula Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol.

[0198] In some embodiments, the solution comprises a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 200 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 200 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 600 mg / ml.

[0199] In some embodiments, the amount of compound Ia or Ib in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 1 w / w% to about 75 w / w. In some embodiments, the amount of compound Ia or Ib in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 9 w / w% to about 75 w / w. In some embodiments, the amount of compound Ia or Ib in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 15 w / w% to about 65 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 20 w / w% to about 55 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 24 w / w% to about 50 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 20 w / w% to about 45 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 25.2 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 25.20 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 41.0 w / w. In some embodiments, the amount of compound of formula Ia or Ib in a solution containing compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 40.92 w / w.

[0200] In some embodiments, the amount of PEG 300 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 15 w / w% to about 90 w / w. In some embodiments, the amount of PEG 300 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 25 w / w% to about 80 w / w. In some embodiments, the amount of PEG 300 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 35 w / w% to about 70 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 40 w / w to about 70 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 40 w / w to about 65 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 46.0 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 45.97 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 62.4 w / w. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 62.39 w / w.

[0201] In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 40 w / w%. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 30 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 20 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 15 w / w%. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 3 w / w% to about 15 w / w%. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 0 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 8.1 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 8.11 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 9.4 w / w. In some embodiments, the amount of water in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 9.41 w / w.

[0202] In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 35 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 25 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 15 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 10 w / w%. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 8 w / w%. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 5 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 0 w / w to about 3 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 0 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 1 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 2 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 3 w / w.In some embodiments, the amount of poloxamer 188 in the solution containing the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 4 w / w.

[0203] In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 30 w / w. In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 25 w / w. In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 15 w / w. In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 10 w / w%. In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 8 w / w%. In some embodiments, the amount of ethanol in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is from about 0 w / w% to about 5 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 0 w / w%, about 1 w / w%, about 2 w / w%, about 3 w / w%, about 4 w / w%, or about 5 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 0 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 1 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 2 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 3 w / w.In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 4 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the compound of formula Ia or Ib, PEG 300, and optionally one, two, or three additional compounds selected from water, poloxamer 188, and ethanol is about 5 w / w.

[0204] In some embodiments, the solution comprises about 20 w / w% to about 55 w / w% of a compound of formula Ia or Ib, about 35 w / w% to about 70 w / w% of PEG 300, about 0 w / w% to about 20 w / w% of water, about 0 w / w% to about 10 w / w% of poloxamer 188, and about 0 w / w% to about 10 w / w% of ethanol. In some embodiments, the solution comprises about 24 w / w% to about 50 w / w% of a compound of formula Ia or Ib, about 40 w / w% to about 65 w / w% of PEG 300, about 0 w / w% to about 15 w / w% of water, about 0 w / w% to about 8 w / w% of poloxamer 188, and about 0 w / w% to about 10 w / w% of ethanol. In some embodiments, the solution comprises about 24 w / w% to about 50 w / w% of a compound of formula Ia or Ib, about 40 w / w% to about 65 w / w% of PEG 300, about 0 w / w% to about 15 w / w% of water, about 0 w / w% to about 8 w / w% of poloxamer 188 and about 0 w / w% to about 5 w / w% of ethanol.

[0205] In some embodiments, the solution comprises about 25.2 w / w% of a compound of formula Ia or Ib, about 62.4 w / w% of PEG 300, about 9.4 w / w% of water, and about 3.0 w / w% of poloxamer 188. In some embodiments, the solution comprises about 25.20 w / w% of a compound of formula Ia or Ib, about 62.39 w / w% of PEG 300, about 9.41 w / w% of water, and about 3.00 w / w% of poloxamer 188. In some embodiments, the solution comprises about 25.2 w / w% of a compound of formula Ib, about 62.4 w / w% of PEG 300, about 9.4 w / w% of water, and about 3.0 w / w% of poloxamer 188. In some embodiments, the solution contains about 25.20 w / w% of the compound of formula Ib, about 62.39 w / w% of PEG 300, about 9.41 w / w% of water and about 3.00 w / w% of poloxamer 188.

[0206] In some embodiments, the solution comprises about 41.0 w / w% of a compound of formula Ia or Ib, about 46.0 w / w% of PEG 300, about 8.1 w / w% of water, and about 5 w / w% of ethanol. In some embodiments, the solution comprises about 40.92 w / w% of a compound of formula Ia or Ib, about 45.97 w / w% of PEG 300, about 8.11 w / w% of water, and about 5 w / w% of ethanol. In some embodiments, the solution comprises about 41.0 w / w% of a compound of formula Ib, about 46.0 w / w% of PEG 300, about 8.1 w / w% of water, and about 5 w / w% of ethanol. In some embodiments, the solution comprises about 40.92 w / w% of a compound of formula Ib, about 45.97 w / w% of PEG 300, about 8.11 w / w% of water, and about 5 w / w% of ethanol.

[0207] In some embodiments, the solution comprises a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol. In some embodiments, the solution comprises a compound of formula Ia, or a pharmaceutically acceptable salt thereof, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol. In some embodiments, the solution comprises a compound of formula Ia, or a pharmaceutically acceptable salt thereof, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol. In some embodiments, the solution comprises a compound of formula Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol.

[0208] In some embodiments, the solution comprises a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 50 mg / ml to about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 75 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 125 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 200 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution comprising a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 600 mg / ml.

[0209] In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0.5 w / w% to about 60 w / w%. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 2 w / w% to about 50 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 2 w / w% to about 35 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution comprising the sodium salt of compound Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 2 w / w% to about 30 w / w%. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution comprising the sodium salt of compound Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 4 w / w% to about 27 w / w.

[0210] In some embodiments, the amount of PEG 300 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 5 w / w% to about 90 w / w. In some embodiments, the amount of PEG 300 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 10 w / w% to about 80 w / w. In some embodiments, the amount of PEG 300 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 20 w / w% to about 75 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 30 w / w to about 65 w / w.

[0211] In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0.5 w / w% to about 60 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 2 w / w% to about 50 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 5 w / w% to about 45 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 10 w / w% to about 40 w / w%. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 14 w / w% to about 31 w / w.

[0212] In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 35 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 25 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 15 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 10 w / w%. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 8 w / w%. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 5 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 0 w / w to about 3 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 0 w / w.

[0213] In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 30 w / w. In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 25 w / w. In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 15 w / w. In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 10 w / w%. In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 8 w / w. In some embodiments, the amount of ethanol in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is from about 0 w / w% to about 5 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 0 w / w%, about 1 w / w%, about 2 w / w%, about 3 w / w%, about 4 w / w%, or about 5 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 0 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 1 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 2 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 3 w / w.In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 4 w / w. In some embodiments, the amount of poloxamer 188 in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and optionally one or two additional compounds selected from poloxamer 188 and ethanol is about 5 w / w.

[0214] In some embodiments, the solution comprises about 2 w / w% to about 35 w / w% of the sodium salt of a compound of formula Ia or Ib, about 20 w / w% to about 75 w / w% of PEG 300, about 10 w / w% to about 40 w / w% of water, about 0 w / w% to about 10 w / w% of poloxamer 188, and about 0 w / w% to about 10 w / w% of ethanol. In some embodiments, the solution comprises about 2 w / w% to about 35 w / w% of the sodium salt of a compound of formula Ia or Ib, about 20 w / w% to about 75 w / w% of PEG 300, about 10 w / w% to about 40 w / w% of water, about 0 w / w% to about 10 w / w% of poloxamer 188, and about 0 w / w% to about 8 w / w% of ethanol. In some embodiments, the solution comprises about 4 w / w% to about 27 w / w% of a sodium salt of a compound of formula Ia or Ib, about 30 w / w% to about 65 w / w% of PEG 300, about 14 w / w% to about 31 w / w% of water, about 0 w / w% to about 8 w / w% of poloxamer 188 and about 0 w / w% to about 5 w / w% of ethanol.

[0215] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solution comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solution comprises a compound of formula Ia, PEG 300, and water. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia, PEG 300, and water. In some embodiments, the solution comprises a compound of formula Ib, PEG 300, and water. In some embodiments, the solution comprises a sodium salt of a compound of formula Ib, PEG 300, and water.

[0216] In some embodiments, the solution comprises a compound of formula Ia or Ib, PEG 300, and water. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, and water is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, and water is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, and water is from about 50 mg / ml to about 400 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, and water is from about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is from about 75 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 75 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 125 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 175 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 200 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 225 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 250 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 275 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 325 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 350 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 375 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 425 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 450 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 475 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is about 600 mg / ml.

[0217] In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 5 w / w% to about 15 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 5 w / w% to about 10 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 8 w / w% to about 12 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 9 w / w% to about 10 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 5 w / w% to about 15 w / w. The water content in the 300 and water solution is approximately 8.0 w / w, approximately 8.1 w / w, approximately 8.2 w / w, approximately 8.3 w / w, approximately 8.4 w / w, approximately 8.5 w / w, approximately 8.6 w / w, approximately 8.7 w / w, approximately 8.8 w / w, approximately 8.9 w / w, approximately 9.0 w / w, approximately 9.1 w / w, approximately 9.2 w / w, approximately 9.3 w / w, approximately 9.4 w / w, approximately 9.5 w / w, approximately 9.6 w / w, approximately 9.7 w / w, approximately 9.8 w / w, approximately 9.9 w / w, and approximately 10.0 w / w. %, approximately 10.1 w / w%, approximately 10.2 w / w%, approximately 10.3 w / w%, approximately 10.4 w / w%, approximately 10.5 w / w%, approximately 10.6 w / w%, approximately 10.7 w / w%, approximately 10.8 w / w%, approximately 10.9 w / w%, approximately 11.0 w / w%, approximately 11.1 w / w%, approximately 11.2 w / w%, approximately 11.3 w / w%, approximately 11.4 w / w%, approximately 11.5 w / w%, approximately 11.6 w / w%, approximately 11.7 w / w%, approximately 11.8 w / w%, approximately 11.9 w / w%, or approximately 12.0 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 9.0 w / w, about 9.1 w / w, about 9.2 w / w, about 9.3 w / w, about 9.4 w / w, about 9.5 w / w, about 9.6 w / w, about 9.7 w / w, about 9.8 w / w, about 9.9 w / w%, or about 10.0 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 9.5 w / w, about 9.6 w / w, about 9.7 w / w, about 9.8 w / w, about 9.9 w / w%, or about 10.0 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 9.8 w / w. In some embodiments, the amount of water in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 10 w / w.

[0218] In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is from about 50 w / w% to about 85 w / w. In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is from about 60 w / w% to about 80 w / w. In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is from about 60 w / w% to about 70 w / w. In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is from about 40 w / w, about 45 w / w, about 50 w / w, about 55 w / w, about 60 w / w, about 65 w / w, about 70 w / w, about 75 w / w, about 80 w / w%, or about 85 w / w. In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 65 w / w. In some embodiments, the amount of PEG 300 in the solution containing the compound of formula Ia or Ib, PEG 300, and water is about 65.0 w / w.

[0219] In some embodiments, the amount of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is from about 15 w / w% to about 35 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is from about 20 w / w% to about 35 w / w. In some embodiments, the amount of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, and water is from about 24 w / w% to about 26 w / w. In some embodiments, the amount of compound Ia or Ib in the solution containing compound Ia or Ib, PEG 300, and water is about 24.5 w / w, about 24.6 w / w, about 24.7 w / w, about 24.8 w / w, about 24.9 w / w, about 25.0 w / w, about 25.1 w / w, about 25.2 w / w, about 25.3 w / w, about 25.4 w / w%, or about 25.5 w / w. In some embodiments, the amount of compound Ia or Ib in the solution containing compound Ia or Ib, PEG 300, and water is about 25 w / w. In some embodiments, the amount of compound Ia or Ib in the solution containing compound Ia or Ib, PEG 300, and water is about 25.2 w / w.

[0220] In some embodiments, the solution comprises about 5 w / w% to about 15 w / w% water, about 50 w / w% to about 85 w / w% PEG 300, and about 15 w / w% to about 35 w / w% of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 5 w / w% to about 10 w / w% water, about 60 w / w% to about 80 w / w% PEG 300, and about 20 w / w% to about 35 w / w% of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 8 w / w% to about 12 w / w% water, about 60 w / w% to about 70 w / w% PEG 300, and about 15 w / w% to about 35 w / w% of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 9 w / w% to about 10 w / w% water, about 60 w / w% to about 70 w / w% PEG 300, and about 24 w / w% to about 26 w / w% of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 9.8 w / w% water, about 65.0 w / w% PEG 300, and about 25.2 w / w% of a compound of formula Ia. In some embodiments, the solution comprises about 10 w / w% water, about 65.0 w / w% PEG 300, and about 25 w / w% of a compound of formula Ia. In some embodiments, the solution comprises about 9.8 w / w% water, about 65.0 w / w% PEG 300, and about 25.2 w / w% of a compound of formula Ib. In some embodiments, the solution comprises about 10 w / w% water, about 65.0 w / w% PEG 300, and about 25 w / w% of a compound of formula Ib. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia or Ib, PEG 300, and water. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is from about 75 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 50 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 75 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 125 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 175 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 200 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 225 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 250 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 275 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 325 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 350 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 375 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 425 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 450 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 475 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 600 mg / ml.

[0221] In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, and water is about 309 mg / ml. In some embodiments, the concentration of compound Ib in a solution containing the sodium salt of compound Ib, PEG 300, and water is about 309 mg / ml.

[0222] In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 10 w / w% to about 40 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 15 w / w% to about 35 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 20 w / w% to about 30 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 21 w / w% to about 29 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 23.4 w / w% to about 27.5 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is about 23.41 w / w% to about 27.47 w / w.In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is approximately 22.0 w / w, approximately 22.1 w / w, approximately 22.2 w / w, approximately 22.3 w / w, approximately 22.4 w / w, approximately 22.5 w / w, approximately 22.6 w / w, approximately 22.7 w / w, approximately 22.8 w / w, approximately 22.9 w / w, approximately 23.0 w / w, approximately 23.1 w / w, approximately 23.2 w / w, approximately 23.3 w / w, approximately 23.4 w / w, approximately 23.5 w / w, and approximately 23.6 w / w. w%, approximately 23.7w / w%, approximately 23.8w / w%, approximately 23.9w / w%, approximately 24.0w / w%, approximately 24.1w / w%, approximately 24.2w / w%, approximately 24.3w / w%, approximately 24.4w / w%, approximately 24.5w / w%, approximately 24.6w / w%, approximately 24.7w / w%, approximately 24.8w / w%, approximately 24.9w / w%, approximately 25.0w / w%, approximately 25.1w / w%, approximately 25.2w / w%, approximately 25.3w / w%, approximately 25.4w / w %, approximately 25.5w / w%, approximately 25.6w / w%, approximately 25.7w / w%, approximately 25.8w / w%, approximately 25.9w / w%, approximately 26.0w / w%, approximately 26.1w / w%, approximately 26.2w / w%, approximately 26.3w / w%, approximately 26.4w / w%, approximately 26.5w / w%, approximately 26.6w / w%, approximately 26.7w / w%, approximately 26.8w / w%, approximately 26.9w / w%, approximately 27.0w / w%, approximately 27.1w / w%, approximately 27.2w / w% Approximately 27.3 w / w%, approximately 27.4 w / w%, approximately 27.5 w / w%, approximately 27.6 w / w%, approximately 27.7 w / w%, approximately 27.8 w / w%, approximately 27.9 w / w%, approximately 28.0 w / w%, approximately 28.1 w / w%, approximately 28.2 w / w%, approximately 28.3 w / w%, approximately 28.4 w / w%, approximately 28.5 w / w%, approximately 28.6 w / w%, approximately 28.7 w / w%, approximately 28.8 w / w%, approximately 28.9 w / w%, or approximately 29.0 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is approximately 23.4 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is approximately 23.41 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is about 27.47 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is about 27.5 w / w.

[0223] In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 21.1 w / w% to about 27.5 w / w%. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is from about 21.13 w / w% to about 27.47 w / w.

[0224] In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is about 21.1 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound Ia or Ib, PEG 300, and water is about 21.13 w / w.

[0225] In some embodiments, the amount of PEG300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is from about 35 w / w% to about 75 w / w. In some embodiments, the amount of PEG300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is from about 45 w / w% to about 65 w / w. In some embodiments, the amount of PEG300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is from about 48 w / w% to about 60 w / w. In some embodiments, the amount of PEG300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is from about 50 w / w% to about 59 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 50.1 w / w% to about 58.8 w / w%. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 50.13 w / w% to about 58.84 w / w. In some embodiments, the amount of PEG 300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is about 45 w / w, about 46 w / w, about 47 w / w, about 48 w / w, about 49 w / w, about 50 w / w, about 51 w / w, about 52 w / w, about 53 w / w, about 54 w / w, about 55 w / w, about 56 w / w, about 57 w / w, about 58 w / w, about 59 w / w, about 60 w / w, about 61 w / w, about 62 w / w, about 63 w / w, about 64 w / w, or about 65 w / w. In some embodiments, the amount of PEG 300 in the solution of the sodium salt of the compound containing formula Ia or Ib, PEG 300, and water is about 50.1 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 50.13 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 58.8 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 58.84 w / w.

[0226] In some embodiments, the amount of PEG300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 45.3 w / w% to about 58.8 w / w%. In some embodiments, the amount of PEG300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 45.25 w / w% to about 58.84 w / w.

[0227] In some embodiments, the amount of PEG300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 45.25 w / w. In some embodiments, the amount of PEG300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is about 45.3 w / w.

[0228] In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 5 w / w% to about 35 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 10 w / w% to about 30 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 11 w / w% to about 28 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 13 w / w% to about 27 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 13.69 w / w% to about 26.46 w / w%. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is from about 13.7 w / w% to about 26.5 w / w%. In some embodiments, the amount of sodium salt of compound Ia or Ib, PEG 300, and water is from about 13.7 w / w% to about 26.5 w / w%. The amount of sodium salt of compound Ia or Ib in a solution of 300 and water is approximately 13.0 w / w%, approximately 13.1 w / w%, approximately 13.2 w / w%, approximately 13.3 w / w%, approximately 13.4 w / w%, approximately 13.5 w / w%, approximately 13.6 w / w%, approximately 13.7 w / w%, approximately 13.8 w / w%, approximately 13.9 w / w%, approximately 14.0 w / w%, approximately 14.1 w / w%, approximately 14.2 w / w%, approximately 14.3 w / w%, approximately 14.4 w / w%, approximately 14.5 w / w%, approximately 14.6 w / w%, approximately 14.7 w / w%, approximately 14.8 w / w%, approximately 14.9 w / w%, approximately 15.0 w / w%, approximately 15.1 w / w%, approximately 15.2 w / w%, and approximately 15.3 w / w%. Approximately 15.4 w / w%, approximately 15.5 w / w%, approximately 15.6 w / w%, approximately 15.7 w / w%, approximately 15.8 w / w%, approximately 15.9 w / w%, approximately 16.0 w / w%, approximately 16.1 w / w%, approximately 16.2 w / w%, approximately 16.3 w / w%, approximately 16.4 w / w%, approximately 16.5 w / w%, approximately 16.6 w / w%, approximately 16.7 w / w%, approximately 16.8 w / w%, approximately 16.9 w / w%, approximately 17.0 w / w%, approximately 17.1 w / w%, approximately 17.2 w / w%, approximately 17.3 w / w%, approximately 17.4 w / w%, approximately 17.5 w / w%, approximately 17.6 w / w%, approximately 17.7 w / w%, approximately 17.8 w / w%, approximately 17.9 w / w%, approximately 18.0w / w%, approximately 18.1w / w%, approximately 18.2w / w%, approximately 18.3w / w%, approximately 18.4w / w%, approximately 18.5w / w%, approximately 18.6w / w%, approximately 18.7w / w%, approximately 18.8w / w%, approximately 18.9w / w%, approximately 19.0w / w%, approximately 19.1w / w%, approximately 19.2w / w%, approximately 19.3w / w%, approximately 19.4w / w%, approximately 19.5w / w%, approximately 19.6w / w%, approximately 19.7w / w%, approximately 19.8w / w%, approximately 19.9w / w%, approximately 20.0w / w%, approximately 21.1w / w%, approximately 21.2w / w%, approximately 21.3w / w%, approximately 21.4w / w%, approximately 21. 5w / w%, approximately 21.6w / w%, approximately 21.7w / w%, approximately 21.8w / w%, approximately 21.9w / w%, approximately 22.0w / w%, approximately 22.1w / w%, approximately 22.2w / w%, approximately 22.3w / w%, approximately 22.4w / w%, approximately 22.5w / w%, approximately 22.6w / w%, approximately 22.7w / w%, approximately 22.8w / w%, approximately 22.9w / w%, approximately 23.0w / w%, approximately 23.1w / w%, approximately 23.2w / w%, approximately 23.3w / w%, approximately 23.4w / w%, approximately 23.5w / w%, approximately 23.6w / w%, approximately 23.7w / w%, approximately 23.8w / w%, approximately 23.9w / w%, approximately 24. 0w / w%, approximately 24.1w / w%, approximately 24.2w / w%, approximately 24.3w / w%, approximately 24.4w / w%, approximately 24.5w / w%, approximately 24.6w / w%, approximately 24.7w / w%, approximately 24.8w / w%, approximately 24.9w / w%, approximately 25.0w / w%, approximately 25.1w / w%, approximately 25.2w / w%, approximately 25.3w / w%, approximately 25.4w / w%, approximately 25.5w / w%, approximately 25.6w / w%, approximately 25.7w / w%, approximately 25.8w / w%, approximately 25.9w / w%, approximately 26.0w / w%, approximately 26.1w / w%, approximately 26.2w / w%, approximately 26.3w / w%, approximately 26.4w / w%, approximately 26. 5w / w%, approximately 26.6w / w%, approximately 26.7w / w%, approximately 26.8w / w%, approximately 26.9w / w%, approximately 27.0w / w%, approximately 27.1w / w%, approximately 27.2w / w%, approximately 27.3w / w%, approximately 27.4w / w%, approximately 27.5w / w%, approximately 27.6w / w%, approximately 27.7w / w%, approximately 27.8w / w%, approximately 27.9w / w%, approximately 28.0w / w%, approximately 28.1w / w%, approximately 28.2w / w%, approximately 28.3w / w%, approximately 28.4w / w%, approximately 28.5w / w%, approximately 28.6w / w%, approximately 28.7w / w%, approximately 28.8w / w%, approximately 28.9w / w%, or approximately 29%.0 w / w%. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 13.69 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 13.7 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 26.46 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 26.5 w / w.

[0229] In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 13.69 w / w% to about 33.61 w / w%. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, and water is from about 13.7 w / w% to about 33.6 w / w.

[0230] In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 33.61 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, and water is about 33.6 w / w.

[0231] In some embodiments, the solution comprises about 10 w / w% to about 40 w / w% water, about 35 w / w% to about 75 w / w% PEG 300, and about 5 w / w% to about 35 w / w% a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 15 w / w% to about 35 w / w% water, about 45 w / w% to about 65 w / w% PEG 300, and about 10 w / w% to about 30 w / w% a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 20 w / w% to about 30 w / w% water, about 48 w / w% to about 60 w / w% PEG 300, and about 11 w / w% to about 28 w / w% a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 21 w / w% to about 29 w / w% of water, about 50 w / w% to about 59 w / w% of PEG 300, and about 13 w / w% to about 27 w / w% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 23.4 w / w% to about 27.5 w / w% of water, about 50.1 w / w% to about 58.8 w / w% of PEG 300, and about 13.7 w / w% to about 26.5 w / w% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 23.41 w / w% to about 27.47 w / w% of water, about 50.13 w / w% to about 58.84 w / w% of PEG 300, and about 13.69 w / w% to about 26.46 w / w% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 27.5 w / w% water, about 58.8 w / w% PEG 300, and about 13.7% sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 27.47 w / w% water, about 58.84 w / w% PEG 300, and about 13.69% sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 23.4 w / w% water, about 50.1 w / w% PEG 300, and about 26.5% sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 23.41 w / w% water, about 50.13 w / w% PEG 300, and about 26.46% sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 27.5 w / w% water, about 58.8 w / w% PEG 300, and about 13.7% sodium salt of the compound of formula Ib. In some embodiments, the solution comprises about 27.47 w / w% water, about 58.84 w / w% PEG 300, and about 13.69% sodium salt of the compound of formula Ib. In some embodiments, the solution comprises about 23.4 w / w% water, about 50.1 w / w% PEG 300, and about 26.5% sodium salt of the compound of formula Ib.In some embodiments, the solution contains about 23.41 w / w% water, about 50.13 w / w% PEG 300 and about 26.46% sodium salt of the compound of formula Ib.

[0232] In some embodiments, the solution comprises about 10 w / w% to about 40 w / w% water, about 35 w / w% to about 75 w / w% PEG 300, and about 5 w / w% to about 45 w / w% a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 10 w / w% to about 30 w / w% water, about 35 w / w% to about 65 w / w% PEG 300, and about 5 w / w% to about 45 w / w% a sodium salt of a compound of formula Ia or Ib.

[0233] In some embodiments, the solution comprises about 21.1 w / w% to about 27.5 w / w% of water, about 45.3 w / w% to about 58.8 w / w% of PEG 300, and about 13.7 w / w% to about 33.6 w / w% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 21.13 w / w% to about 27.47 w / w% of water, about 45.25 w / w% to about 58.84 w / w% of PEG 300, and about 13.69 w / w% to about 33.61 w / w% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 21.1 w / w% of water, about 45.3 w / w% of PEG 300, and about 33.6% of a sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 21.13 w / w% water, about 45.25 w / w% PEG 300, and about 33.61% sodium salt of a compound of formula Ia or Ib. In some embodiments, the solution comprises about 21.1 w / w% water, about 45.3 w / w% PEG 300, and about 33.6% sodium salt of a compound of formula Ib. In some embodiments, the solution comprises about 21.13 w / w% water, about 45.25 w / w% PEG 300, and about 33.61% sodium salt of a compound of formula Ib.

[0234] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG300, water, and ethanol. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG300, water, and ethanol. In some embodiments, the solution comprises a compound of formula Ia, PEG 300, water, and ethanol. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia, PEG 300, water, and ethanol. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG 300, water, and ethanol. In some embodiments, the solution comprises a compound of formula Ib, PEG 300, water, and ethanol. In some embodiments, the solution comprises a sodium salt of a compound of formula Ib, PEG 300, water, and ethanol.

[0235] In some embodiments, the solution comprises a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 200 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 200 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 250 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 350 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 450 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 550 mg / ml.In some embodiments, the concentration of the compound of formula Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 600 mg / ml.

[0236] In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 10 w / w to about 20 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 12 w / w to about 20 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 16.93 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 16.9 w / w.

[0237] In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is about 30 w / w to about 40 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is about 32 w / w to about 40 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is about 36.22 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, and ethanol is about 36.2 w / w.

[0238] In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, and ethanol is from about 35 w / w% to about 45 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, and ethanol is from about 37 w / w% to about 45 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, and ethanol is about 41.85 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, and ethanol is about 41.9 w / w.

[0239] In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 0.1 w / w% to about 10 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 1 w / w% to about 9 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is from about 3 w / w% to about 8 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 5.00 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, and ethanol is about 5.0 w / w.

[0240] In some embodiments, the solution comprises about 10 w / w% to about 40 w / w% water, about 20 w / w% to about 75 w / w% PEG 300, about 10 w / w% to about 70 w / w% sodium salt of a compound of formula Ia or Ib, and about 1 w / w% to about 9 w / w% ethanol. In some embodiments, the solution comprises about 10 w / w% to about 20 w / w% water, about 30 w / w% to about 40 w / w% PEG 300, about 37 w / w% to about 45 w / w% sodium salt of a compound of formula Ia or Ib, and about 3 w / w% to about 8 w / w% ethanol.

[0241] In some embodiments, the solution comprises about 16.93 w / w% water, about 36.22 w / w% PEG 300, about 41.85% sodium salt of the compound of formula Ia or Ib, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 16.9 w / w% water, about 36.2 w / w% PEG 300, about 41.9% sodium salt of the compound of formula Ia or Ib, and about 5.0 w / w% ethanol. In some embodiments, the solution comprises about 16.93 w / w% water, about 36.22 w / w% PEG 300, about 41.85% sodium salt of the compound of formula Ib, and about 5.00 w / w% ethanol. In some embodiments, the solution contains about 16.9 w / w% water, about 36.2 w / w% PEG 300, about 41.9% sodium salt of the compound of formula Ib, and about 5.0 w / w% ethanol.

[0242] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a compound of formula Ia, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a compound of formula Ib, PEG 300, poloxamer 188, and water. In some embodiments, the solution comprises a sodium salt of a compound of formula Ib, PEG 300, poloxamer 188, and water.

[0243] In some embodiments, the solution comprises a sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 50 mg / ml to about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 75 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 75 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 125 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 175 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188 and water is about 200 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 225 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 250 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 275 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 325 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 350 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 375 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 425 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 450 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 475 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188 and water is about 600 mg / ml.

[0244] In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 10 w / w% to about 45 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 15 w / w% to about 35 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 20 w / w% to about 35 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 20 w / w% to about 31 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 21.9 w / w% to about 30.1 w / w%. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 21.87 w / w% to about 30.07 w / w%. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 21.9 w / w% to about 30.1 w / w%. The water content in the solution of 300, poloxamer 188, and water was approximately 19.0 w / w, approximately 19.1 w / w, approximately 19.2 w / w, approximately 19.3 w / w, approximately 19.4 w / w, approximately 19.5 w / w, approximately 19.6 w / w, approximately 19.7 w / w, approximately 19.8 w / w, approximately 19.9 w / w, approximately 20.0 w / w, and approximately 20.1 w / w. w%, approximately 20.2w / w%, approximately 20.3w / w%, approximately 20.4w / w%, approximately 20.5w / w%, approximately 20.6w / w%, approximately 20.7w / w%, approximately 20.8w / w%, approximately 20.9w / w%, approximately 21.0w / w%, approximately 21.1w / w%, approximately 21.2w / w%, approximately 21.3w / w%, approximately 21.4w / w%, approximately 21.5w / w%, approximately 21.6w / w%, approximately 21.7w / w%, approximately 21.8w / w%, approximately 21.9w / w%, approximately 22.0w / w%, approximately 22.1w / w%, approximately 22.2w / w%, approximately 22.3w / w%, approximately 22.4w / w%, approximately 22.5w / w%, approximately 22.6w / w%, approximately 22.7w / w%, approximately 22.8w / w%, approximately 22.9 w / w%, approximately 23.0 w / w%, approximately 23.1 w / w%, approximately 23.2 w / w%, approximately 23.3 w / w%, approximately 23.4 w / w%, approximately 23.5 w / w%, approximately 23.6 w / w%, approximately 23.7 w / w%, approximately 23.8 w / w%, approximately 23.9 w / w%, approximately 24.0 w / w%, approximately 24.1 w / w%, approximately 24.2 w / w%, approximately 24.3w / w%, approximately 24.4w / w%, approximately 24.5w / w%, approximately 24.6w / w%, approximately 24.7w / w%, approximately 24.8w / w%, approximately 24.9w / w%, approximately 25.0w / w%, approximately 25.1w / w%, approximately 25.2w / w%, approximately 25.3w / w%, approximately 25.4w / w%, approximately 25.5w / w%, approximately 25.6w / w%, approximately 25.7w / w%, approximately 25.8w / w%, approximately 25.9w / w%, approximately 26.0w / w%, approximately 26.1w / w%, approximately 26.2w / w%, approximately 26.3w / w%, approximately 26.4w / w%, approximately 26 0.5w / w%, approximately 26.6w / w%, approximately 26.7w / w%, approximately 26.8w / w%, approximately 26.9w / w%, approximately 27.0w / w%, approximately 27.1w / w%, approximately 27.2w / w%, approximately 27.3w / w%, approximately 27.4w / w%, approximately 27.5w / w%, approximately 27.6w / w%, approximately 27.7w / w%, approximately 27.8w / w%, approximately 27.9w / w%, approximately 28.0w / w%, approximately 28.1w / w%, approximately 28.2w / w%, approximately 28.3w / w%, approximately 28.4w / w%, approximately 28.5w / w%, approximately 28.6w / w%, approximately 2 8.7w / w%, approximately 28.8w / w%, approximately 28.9w / w%, approximately 29.0w / w%, approximately 29.1w / w%, approximately 29.2w / w%, approximately 29.3w / w%, approximately 29.4w / w%, approximately 29.5w / w%, approximately 29.6w / w%, approximately 29.7w / w%, approximately 29.8w / w%, approximately 29.9w / w%, approximately 30.0w / w%, approximately 30.1w / w%, approximately 30.2w / w%, approximately 30.3w / w%, approximately 30.4w / w%, approximately 30.5w / w%, approximately 30.6w / w%, approximately 30.7w / w%, approximately 30.8w / w%, approximately 30.9 w / w%, approximately 31.0 w / w%, approximately 31.1 w / w%, approximately 31.2 w / w%, approximately 31.3 w / w%, approximately 31.4 w / w%, approximately 31.5 w / w%, approximately 31.6 w / w%, approximately 31.7 w / w%, approximately 31.8 w / w%, approximately 31.9 w / w%, approximately 32.0 w / w%, approximately 32.1 w / w%, approximately 32.2 w / w%, approximately 32.3 w / w%, approximately 32.4 w / w%, approximately 32.5 w / w%, approximately 32.6 w / w%, approximately 32.7 w / w%, approximately 32.8 w / w%, approximately 32.9 w / w%, or approximately 33.0 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 21.87 w / w%.9 w / w%. In some embodiments, the amount of water in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26.68 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26.7 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 27.5 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 27.51 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 28.36 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 28.4 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 29.2 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 29.21 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 30.07 w / w%. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 30.1 w / w%.

[0245] In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 19.18 w / w% to about 30.07 w / w%. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 19.2 w / w% to about 30.1 w / w.

[0246] In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 19.18 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 19.2 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 20.16 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 20.2 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.10 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.1 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.48 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.5 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.85 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 22.9 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 23.2 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26.79 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26.8 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 27.61 w / w. In some embodiments, the amount of water in a solution comprising the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 27.6 w / w.In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 28.43 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 28.4 w / w.

[0247] In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 30 w / w% to about 85 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 35 w / w% to about 75 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 40 w / w% to about 70 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 45 w / w% to about 68 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 46.8 w / w% to about 64.4 w / w%. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 46.84 w / w% to about 64.40 w / w%. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is... The amount of 300 is approximately 40 w / w, approximately 41 w / w, approximately 42 w / w, approximately 43 w / w, approximately 44 w / w, approximately 45 w / w, approximately 46 w / w, approximately 47 w / w, approximately 48 w / w, approximately 49 w / w, approximately 50 w / w, approximately 51 w / w, approximately 52 w / w, approximately 53 w / w, approximately 54 w / w, approximately 55 w / w, approximately 56 w / w, approximately 57 w / w, approximately 58 w / w, approximately 59 w / w, approximately 60 w / w, approximately 61 w / w, approximately 62 w / w, approximately 63 w / w, approximately 64 w / w, approximately 65 w / w, approximately 66 w / w, approximately 67 w / w, approximately 68 w / w, approximately 69 w / w, or approximately 70 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 46.8 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 46.84 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 57.1 w / w.In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 57.13 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 58.9 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 58.92 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 60.7 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 60.73 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 62.55 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 62.6 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 64.4 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188 and water is about 64.40 w / w.

[0248] In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 41.09 w / w% to about 64.40 w / w%. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 41.1 w / w% to about 64.4 w / w.

[0249] In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 41.09 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 41.1 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 43.17 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 43.2 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 47.33 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 47.3 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 48.13 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 48.1 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 48.94 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 48.9 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 49.73 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 49.7 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 57.38 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 57.4 w / w.In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 59.13 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 59.1 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 60.90 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 60.9 w / w.

[0250] In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.5 w / w% to about 40 w / w%. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 1 w / w% to about 35 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 1 w / w% to about 30 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 3 w / w% to about 28 w / w%. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 4 w / w% to about 27 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is from about 4.68 w / w% to about 26.47 w / w. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in a solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.7 w / w% to about 26.5 w / w%. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.7 w / w% to about 26.5 w / w%. The amount of sodium salt of compound Ia or Ib in a solution of 300, poloxamer 188, and water is approximately 3.0 w / w%, approximately 3.1 w / w%, approximately 3.2 w / w%, approximately 3.3 w / w%, approximately 3.4 w / w%, approximately 3.5 w / w%, approximately 3.6 w / w%, approximately 3.7 w / w%, approximately 3.8 w / w%, approximately 3.9 w / w%, approximately 4.0 w / w%, approximately 4.1 w / w%, approximately 4.2 w / w%, approximately 4.3 w / w%, approximately 4.4 w / w%, approximately 4.5 w / w%, approximately 4.6 w / w%, approximately 4.7 w / w%, approximately 4.8 w / w%, approximately 4. 9w / w%, approximately 5.0w / w%, approximately 5.1w / w%, approximately 5.2w / w%, approximately 5.3w / w%, approximately 5.4w / w%, approximately 5.5w / w%, approximately 5.6w / w%, approximately 5.7w / w%, approximately 5.8w / w%, approximately 5.9w / w%, approximately 6.0w / w%, approximately 6.1w / w%, approximately 6.2w / w%, approximately 6.3w / w%, approximately 6.4w / w%, approximately 6.5w / w%, approximately 6.6w / w%, approximately 6.7w / w%, approximately 6.8w / w%, approximately 6.9w / w%, approximately 7.0w / w%, approximately 7.1w / w%, approximately 7.2w / w%, approximately 7.3w / w%, approximately 7.4w / w%, approximately 7.5w / w%, approximately 7.6w / w%, approximately 7.7w / w%, approximately 7.8w / w%, approximately 7.9w / w%, approximately 8.0w / w%, approximately 8.1w / w%, approximately 8.2w / w%, approximately 8.3w / w%, approximately 8.4w / w%, approximately 8.5w / w%, approximately 8.6w / w%, approximately 8.7w / w%, approximately 8.8w / w%, approximately 8.9w / w%, approximately 9.0w / w%, approximately 9.1w / w%, approximately 9.2w / w%, approximately 9.3w / w%, approximately 9.4w / w%, approximately 9.5w / w%, approximately 9.6w / w%, approximately 9.7w / w%, approximately 9.8w / w%, approximately 9.9w / w% Approximately 10.0 w / w%, approximately 10.1 w / w%, approximately 10.2 w / w%, approximately 10.3 w / w%, approximately 10.4 w / w%, approximately 10.5 w / w%, approximately 10.6 w / w%, approximately 10.7 w / w%, approximately 10.8 w / w%, approximately 10.9 w / w%, approximately 11.0 w / w%, approximately 11.1 w / w%, approximately 11.2 w / w%, approximately 11.3 w / w%, approximately 11.4 w / w%, approximately 11.5 w / w%, approximately 11.6 w / w%, approximately 11.7 w / w%, approximately 11.8 w / w%, approximately 11.9 w / w%, approximately 12.0 w / w%, approximately 12.1 w / w%, approximately 12.2 w / w%, approximately 12.3 w / w%, approximately 12.4 w / w w%, approximately 12.5w / w%, approximately 12.6w / w%, approximately 12.7w / w%, approximately 12.8w / w%, approximately 12.9w / w%, approximately 13.0w / w%, approximately 13.1w / w%, approximately 13.2w / w%, approximately 13.3w / w%, approximately 13.4w / w%, approximately 13.5w / w%, approximately 13.6w / w%, approximately 13.7w / w%, approximately 13.8w / w%, approximately 13.9w / w%, approximately 14.0w / w%, approximately 14.1w / w%, approximately 14.2w / w%, approximately 14.3w / w%, approximately 14.4w / w%, approximately 14.5w / w%, approximately 14.6w / w%, approximately 14.7w / w%, approximately 14.8w / w%, approximately 14.9 w / w%, approximately 15.0 w / w%, approximately 15.1 w / w%, approximately 15.2 w / w%, approximately 15.3 w / w%, approximately 15.4 w / w%, approximately 15.5 w / w%, approximately 15.6 w / w%, approximately 15.7 w / w%, approximately 15.8 w / w%, approximately 15.9 w / w%, approximately 16.0 w / w%, approximately 16.1 w / w%, approximately 16.2 w / w%, approximately 16.3 w / w%, approximately 16.4 w / w%, approximately 16.5 w / w%, approximately 16.6 w / w%, approximately 16.7 w / w%, approximately 16.8 w / w%, approximately 16.9 w / w%, approximately 17.0 w / w%, approximately 17.1 w / w%, approximately 17.2 w / w%, approximately 17.3 w / w%, approximately 17.4w / w%, approximately 17.5w / w%, approximately 17.6w / w%, approximately 17.7w / w%, approximately 17.8w / w%, approximately 17.9w / w%, approximately 18.0w / w%, approximately 18.1w / w%, approximately 18.2w / w%, approximately 18.3w / w%, approximately 18.4w / w%, approximately 18.5w / w%, approximately 18.6w / w%, approximately 18.7w / w%, approximately 18.8w / w%, approximately 18.9w / w%, approximately 19.0w / w%, approximately 19.1w / w%, approximately 19.2w / w%, approximately 19.3w / w%, approximately 19.4w / w%, approximately 19.5w / w%, approximately 19.6w / w%, approximately 19.7w / w%, approximately 19.8w / w%, approximately 19. 9w / w%, approximately 20.0w / w%, approximately 20.1w / w%, approximately 20.2w / w%, approximately 20.3w / w%, approximately 20.4w / w%, approximately 20.5w / w%, approximately 20.6w / w%, approximately 20.7w / w%, approximately 20.8w / w%, approximately 20.9w / w%, approximately 21.0w / w%, approximately 21.1w / w%, approximately 21.2w / w%, approximately 21.3w / w%, approximately 21.4w / w%, approximately 21.5w / w%, approximately 21.6w / w%, approximately 21.7w / w%, approximately 21.8w / w%, approximately 21.9w / w%, approximately 22.0w / w%, approximately 22.1w / w%, approximately 22.2w / w%, approximately 22.3w / w%, approximately 22. 4w / w%, approximately 22.5w / w%, approximately 22.6w / w%, approximately 22.7w / w%, approximately 22.8w / w%, approximately 22.9w / w%, approximately 23.0w / w%, approximately 23.1w / w%, approximately 23.2w / w%, approximately 23.3w / w%, approximately 23.4w / w%, approximately 23.5w / w%, approximately 23.6w / w%, approximately 23.7w / w%, approximately 23.8w / w%, approximately 23.9w / w%, approximately 24.0w / w%, approximately 24.1w / w%, approximately 24.2w / w%, approximately 24.3w / w%, approximately 24.4w / w%, approximately 24.5w / w%, approximately 24.6w / w%, approximately 24.7w / w%, approximately 24.8w / w%, approximately 24. 9w / w%, approximately 25.0w / w%, approximately 25.1w / w%, approximately 25.2w / w%, approximately 25.3w / w%, approximately 25.4w / w%, approximately 25.5w / w%, approximately 25.6w / w%, approximately 25.7w / w%, approximately 25.8w / w%, approximately 25.9w / w%, approximately 26.0w / w%, approximately 26.1w / w%, approximately 26.2w / w%, approximately 26.3w / w%, approximately 26.4w / w%, approximately 26.5w / w%, approximately 26.6w / w%, approximately 26.7w / w%, approximately 26.8w / w%, approximately 26.9w / w%, approximately 27.0w / w%, approximately 27.1w / w%, approximately 27.2w / w%, approximately 27.3w / w%, approximately 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w%, or about 29.0 w / w. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.68 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 4.7 w / w. In some embodiments, the amount of sodium salt of compound Ia in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 6.97 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 7 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 9.2 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 9.23 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 11.48 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 11.5 w / w. In some embodiments, the amount of sodium salt of compound Ia in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 13.7 w / w. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 13.70 w / w%. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26%.47 w / w%. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 26.5 w / w%.

[0251] In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 4.68 w / w% to about 33.61 w / w%. In some embodiments, the amount of the sodium salt of the compound of formula Ia or Ib in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 4.7 w / w% to about 33.6 w / w.

[0252] In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 9.03 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 9.0 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 11.22 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 11.2 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 13.39 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 13.4 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 25.85 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in a solution containing sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 25.87 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 25.9 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 33.61 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, poloxamer 188, and water is about 33.6 w / w.

[0253] In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.1 w / w% to about 10 w / w%. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.3 w / w% to about 8 w / w%. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.5 w / w% to about 7 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.6 w / w% to about 7 w / w. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.85 w / w% to about 4.82 w / w%. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.9 w / w% to about 4.8 w / w.In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 0.5 w / w, about 0.6 w / w, about 0.7 w / w, about 0.8 w / w, about 0.9 w / w, about 1.0 w / w, about 1.1 w / w, about 1.2 w / w, about 1.3 w / w, about 1.4 w / w, about 1.5 w / w, about 1.6 w / w, about 1.7 w / w, about 1.8 w / w, about 1 0.9w / w%, approximately 2.0w / w%, approximately 2.1w / w%, approximately 2.2w / w%, approximately 2.3w / w%, approximately 2.4w / w%, approximately 2.5w / w%, approximately 2.6w / w%, approximately 2.7w / w%, approximately 2.8w / w%, approximately 2.9w / w%, approximately 3.0w / w%, approximately 3.1w / w%, approximately 3.2w / w%, approximately 3.3w / w%, approximately 3.4w / w%, approximately 3.5w / w%, approximately 3.6 w / w%, approximately 3.7w / w%, approximately 3.8w / w%, approximately 3.9w / w%, approximately 4.0w / w%, approximately 4.1w / w%, approximately 4.2w / w%, approximately 4.3w / w%, approximately 4.4w / w%, approximately 4.5w / w%, approximately 4.6w / w%, approximately 4.7w / w%, approximately 4.8w / w%, approximately 4.9w / w%, approximately 5.0w / w%, approximately 5.1w / w%, approximately 5.2w / w%, approximately 5.3w / w w%, approximately 5.4 w / w%, approximately 5.5 w / w%, approximately 5.6 w / w%, approximately 5.7 w / w%, approximately 5.8 w / w%, approximately 5.9 w / w%, approximately 6.0 w / w%, approximately 6.1 w / w%, approximately 6.2 w / w%, approximately 6.3 w / w%, approximately 6.4 w / w%, approximately 6.5 w / w%, approximately 6.6 w / w%, approximately 6.7 w / w%, approximately 6.8 w / w%, approximately 6.9 w / w%, or approximately 7.0 w / w. In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is approximately 0.85 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 0.9 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.27 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.3 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.68 w / w.In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.7 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.09 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.1 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.49 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.5 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.8 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.82 w / w.

[0254] In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.85 w / w% to about 6.12 w / w%. In some embodiments, the amount of poloxamer 188 in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is from about 0.9 w / w% to about 6.1 w / w.

[0255] In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.18 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.2 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.64 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 1.6 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.04 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.0 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.36 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.44 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 2.4 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 3.06 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 3.1 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 3.54 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 3.5 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.72 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 4.7 w / w.In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 6.12 w / w. In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, poloxamer 188, and water is about 6.1 w / w.

[0256] In some embodiments, the solution comprises about 10 w / w% to about 45 w / w% water, about 30 w / w% to about 85 w / w% PEG 300, about 0.5 w / w% to about 40 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.1 w / w% to about 10 w / w% poloxamer 188. In some embodiments, the solution comprises about 15 w / w% to about 35 w / w% water, about 35 w / w% to about 75 w / w% PEG 300, about 1 w / w% to about 35 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.3 w / w% to about 8 w / w% poloxamer 188. In some embodiments, the solution comprises about 20 w / w% to about 35 w / w% water, about 40 w / w% to about 70 w / w% PEG 300, about 1 w / w% to about 30 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.5 w / w% to about 7 w / w% poloxamer 188. In some embodiments, the solution comprises about 20 w / w% to about 31 w / w% water, about 45 w / w% to about 68 w / w% PEG 300, about 3 w / w% to about 28 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.6 w / w% to about 7 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.9 w / w% to about 30.1 w / w% of water, about 46.8 w / w% to about 64.4 w / w% of PEG 300, about 4.7 w / w% to about 26.5 w / w% of the sodium salt of a compound of formula Ia or Ib, and about 0.9 w / w% to about 4.8 w / w% of poloxamer 188. In some embodiments, the solution comprises about 21.87 w / w% to about 30.07 w / w% of water, about 46.84 w / w% to about 64.40 w / w% of PEG 300, about 4.68 w / w% to about 26.47 w / w% of the sodium salt of a compound of formula Ia or Ib, and about 0.85 w / w% to about 4.82 w / w% of poloxamer 188.

[0257] In some embodiments, the solution comprises about 30.1 w / w% water, about 64.4 w / w% PEG 300, about 4.7 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.9 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.07 w / w% water, about 64.40 w / w% PEG 300, about 4.68 w / w% sodium salt of a compound of formula Ia or Ib, and about 0.85 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.1 w / w% water, about 64.4 w / w% PEG 300, about 4.7 w / w% sodium salt of a compound of formula Ib, and about 0.9 w / w% poloxamer 188. In some embodiments, the solution contains about 30.07 w / w% water, about 64.40 w / w% PEG 300, about 4.68 w / w% sodium salt of the compound of formula Ib, and about 0.85 w / w% poloxamer 188.

[0258] In some embodiments, the solution comprises about 29.2 w / w% water, about 62.6 w / w% PEG 300, about 7 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.3 w / w% poloxamer 188. In some embodiments, the solution comprises about 29.21 w / w% water, about 62.55 w / w% PEG 300, about 6.97 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.27 w / w% poloxamer 188. In some embodiments, the solution comprises about 29.2 w / w% water, about 62.6 w / w% PEG 300, about 7 w / w% sodium salt of a compound of formula Ib, and about 1.3 w / w% poloxamer 188. In some embodiments, the solution contains about 29.21 w / w% water, about 62.55 w / w% PEG 300, about 6.97 w / w% sodium salt of the compound of formula Ib, and about 1.27 w / w% poloxamer 188.

[0259] In some embodiments, the solution comprises about 28.4 w / w% water, about 60.7 w / w% PEG 300, about 9.2 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.7 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.36 w / w% water, about 60.73 w / w% PEG 300, about 9.23 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.68 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.4 w / w% water, about 60.7 w / w% PEG 300, about 9.2 w / w% sodium salt of a compound of formula Ib, and about 1.7 w / w% poloxamer 188. In some embodiments, the solution contains about 28.36 w / w% water, about 60.73 w / w% PEG 300, about 9.23 w / w% sodium salt of the compound of formula Ib, and about 1.68 w / w% poloxamer 188.

[0260] In some embodiments, the solution comprises about 27.5 w / w% water, about 58.9 w / w% PEG 300, about 11.5 w / w% sodium salt of a compound of formula Ia or Ib, and about 2.1 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.51 w / w% water, about 58.92 w / w% PEG 300, about 11.48 w / w% sodium salt of a compound of formula Ia or Ib, and about 2.09 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.5 w / w% water, about 58.9 w / w% PEG 300, about 11.5 w / w% sodium salt of a compound of formula Ib, and about 2.1 w / w% poloxamer 188. In some embodiments, the solution contains about 27.51 w / w% water, about 58.92 w / w% PEG 300, about 11.48 w / w% sodium salt of the compound of formula Ib, and about 2.09 w / w% poloxamer 188.

[0261] In some embodiments, the solution comprises about 26.7 w / w% water, about 57.1 w / w% PEG 300, about 13.7 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.5 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.68 w / w% water, about 57.13 w / w% PEG 300, about 13.70 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.49 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.7 w / w% water, about 57.1 w / w% PEG 300, about 13.7 w / w% a sodium salt of a compound of formula Ib, and about 2.5 w / w% poloxamer 188. In some embodiments, the solution contains about 26.68 w / w% water, about 57.13 w / w% PEG 300, about 13.70 w / w% sodium salt of the compound of formula Ib, and about 2.49 w / w% poloxamer 188.

[0262] In some embodiments, the solution comprises about 21.9 w / w% water, about 46.8 w / w% PEG 300, about 26.5 w / w% sodium salt of a compound of formula Ia or Ib, and about 4.8 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.87 w / w% water, about 46.84 w / w% PEG 300, about 26.47 w / w% sodium salt of a compound of formula Ia or Ib, and about 4.82 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.9 w / w% water, about 46.8 w / w% PEG 300, about 26.5 w / w% sodium salt of a compound of formula Ib, and about 4.8 w / w% poloxamer 188. In some embodiments, the solution contains about 21.87 w / w% water, about 46.84 w / w% PEG 300, about 26.47 w / w% sodium salt of the compound of formula Ib, and about 4.82 w / w% poloxamer 188.

[0263] In some embodiments, the solution comprises about 19.2 w / w% to about 30.1 w / w% of water, about 41.1 w / w% to about 64.4 w / w% of PEG 300, about 4.7 w / w% to about 33.6 w / w% of the sodium salt of a compound of formula Ia or Ib, and about 0.9 w / w% to about 6.1 w / w% of poloxamer 188. In some embodiments, the solution comprises about 19.18 w / w% to about 30.07 w / w% of water, about 41.09 w / w% to about 64.40 w / w% of PEG 300, about 4.68 w / w% to about 33.61 w / w% of the sodium salt of a compound of formula Ia or Ib, and about 0.85 w / w% to about 6.12 w / w% of poloxamer 188.

[0264] In some embodiments, the solution comprises about 28.4 w / w% water, about 60.9 w / w% PEG 300, about 9.0 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.6 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.43 w / w% water, about 60.90 w / w% PEG 300, about 9.03 w / w% sodium salt of a compound of formula Ia or Ib, and about 1.64 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.4 w / w% water, about 60.9 w / w% PEG 300, about 9.0 w / w% sodium salt of a compound of formula Ib, and about 1.6 w / w% poloxamer 188. In some embodiments, the solution contains about 28.43 w / w% water, about 60.90 w / w% PEG 300, about 9.03 w / w% sodium salt of the compound of formula Ib, and about 1.64 w / w% poloxamer 188.

[0265] In some embodiments, the solution comprises about 27.6 w / w% water, about 59.1 w / w% PEG 300, about 11.2 w / w% sodium salt of a compound of formula Ia or Ib, and about 2.0 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.61 w / w% water, about 59.13 w / w% PEG 300, about 11.22 w / w% sodium salt of a compound of formula Ia or Ib, and about 2.04 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.6 w / w% water, about 59.1 w / w% PEG 300, about 11.2 w / w% sodium salt of a compound of formula Ib, and about 2.0 w / w% poloxamer 188. In some embodiments, the solution contains about 27.61 w / w% water, about 59.13 w / w% PEG 300, about 11.22 w / w% sodium salt of the compound of formula Ib, and about 2.04 w / w% poloxamer 188.

[0266] In some embodiments, the solution comprises about 26.8 w / w% water, about 57.4 w / w% PEG 300, about 13.4 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.4 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.79 w / w% water, about 57.38 w / w% PEG 300, about 13.39 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.44 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.8 w / w% water, about 57.4 w / w% PEG 300, about 13.4 w / w% a sodium salt of a compound of formula Ib, and about 2.4 w / w% poloxamer 188. In some embodiments, the solution contains about 26.79 w / w% water, about 57.38 w / w% PEG 300, about 13.39 w / w% sodium salt of the compound of formula Ib, and about 2.44 w / w% poloxamer 188.

[0267] In some embodiments, the solution comprises about 23.2 w / w% water, about 49.7 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ia or Ib, and about 1.2 w / w% poloxamer 188. In some embodiments, the solution comprises about 23.22 w / w% water, about 49.73 w / w% PEG 300, about 25.87 w / w% a sodium salt of a compound of formula Ia or Ib, and about 1.18 w / w% poloxamer 188. In some embodiments, the solution comprises about 23.2 w / w% water, about 49.7 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ib, and about 1.2 w / w% poloxamer 188. In some embodiments, the solution contains about 23.22 w / w% water, about 49.73 w / w% PEG 300, about 25.87 w / w% sodium salt of the compound of formula Ib, and about 1.18 w / w% poloxamer 188.

[0268] In some embodiments, the solution comprises about 22.9 w / w% water, about 48.9 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.4 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.85 w / w% water, about 48.94 w / w% PEG 300, about 25.85 w / w% a sodium salt of a compound of formula Ia or Ib, and about 2.36 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.9 w / w% water, about 48.9 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ib, and about 2.4 w / w% poloxamer 188. In some embodiments, the solution contains about 22.85 w / w% water, about 48.94 w / w% PEG 300, about 25.85 w / w% sodium salt of the compound of formula Ib, and about 2.36 w / w% poloxamer 188.

[0269] In some embodiments, the solution comprises about 22.5 w / w% water, about 48.1 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ia or Ib, and about 3.5 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.48 w / w% water, about 48.13 w / w% PEG 300, about 25.85 w / w% a sodium salt of a compound of formula Ia or Ib, and about 3.54 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.5 w / w% water, about 48.1 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ib, and about 3.5 w / w% poloxamer 188. In some embodiments, the solution contains about 22.48 w / w% water, about 48.13 w / w% PEG 300, about 25.85 w / w% sodium salt of the compound of formula Ib, and about 3.54 w / w% poloxamer 188.

[0270] In some embodiments, the solution comprises about 22.1 w / w% water, about 47.3 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ia or Ib, and about 4.7 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.10 w / w% water, about 47.33 w / w% PEG 300, about 25.85 w / w% a sodium salt of a compound of formula Ia or Ib, and about 4.72 w / w% poloxamer 188. In some embodiments, the solution comprises about 22.1 w / w% water, about 47.3 w / w% PEG 300, about 25.9 w / w% a sodium salt of a compound of formula Ib, and about 4.7 w / w% poloxamer 188. In some embodiments, the solution contains about 22.10 w / w% water, about 47.33 w / w% PEG 300, about 25.85 w / w% sodium salt of the compound of formula Ib, and about 4.72 w / w% poloxamer 188.

[0271] In some embodiments, the solution comprises about 20.2 w / w% water, about 43.2 w / w% PEG 300, about 33.6 w / w% a sodium salt of a compound of formula Ia or Ib, and about 3.1 w / w% poloxamer 188. In some embodiments, the solution comprises about 20.16 w / w% water, about 43.17 w / w% PEG 300, about 33.61 w / w% a sodium salt of a compound of formula Ia or Ib, and about 3.06 w / w% poloxamer 188. In some embodiments, the solution comprises about 20.2 w / w% water, about 43.2 w / w% PEG 300, about 33.6 w / w% a sodium salt of a compound of formula Ib, and about 3.1 w / w% poloxamer 188. In some embodiments, the solution contains about 20.16 w / w% water, about 43.17 w / w% PEG 300, about 33.61 w / w% sodium salt of the compound of formula Ib, and about 3.06 w / w% poloxamer 188.

[0272] In some embodiments, the solution comprises about 19.2 w / w% water, about 41.1 w / w% PEG 300, about 33.6 w / w% a sodium salt of a compound of formula Ia or Ib, and about 6.1 w / w% poloxamer 188. In some embodiments, the solution comprises about 19.18 w / w% water, about 41.09 w / w% PEG 300, about 33.61 w / w% a sodium salt of a compound of formula Ia or Ib, and about 6.12 w / w% poloxamer 188. In some embodiments, the solution comprises about 19.2 w / w% water, about 41.1 w / w% PEG 300, about 33.6 w / w% a sodium salt of a compound of formula Ib, and about 6.1 w / w% poloxamer 188. In some embodiments, the solution contains about 19.18 w / w% water, about 41.09 w / w% PEG 300, about 33.61 w / w% sodium salt of the compound of formula Ib, and about 6.12 w / w% poloxamer 188.

[0273] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ia, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a sodium salt of a compound of formula Ia, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG300, water, poloxamer 188, and ethanol. In some embodiments, the solution contains a sodium salt of the compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG 300, water, poloxamer 188, and ethanol.

[0274] In some embodiments, the solution comprises a sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising a sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 200 mg / ml to about 600 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 300 mg / ml to about 600 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 300 mg / ml to about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 200 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 250 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 300 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 350 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 400 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 450 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 500 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing a sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 550 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 600 mg / ml.

[0275] In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 10 w / w% to about 40 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 10 w / w% to about 20 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 10 w / w% to about 19 w / w. In some embodiments, the amount of water in the solution comprising the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 14.50 w / w% to about 17.26 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 14.5 w / w to about 17.3 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 14.50 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 14.5 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 14.57 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 14.6 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 15.71 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 15.7 w / w. In some embodiments, the amount of water in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 17.26 w / w. In some embodiments, the amount of water in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188 and ethanol is about 17.3 w / w.

[0276] In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 20 w / w to about 75 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 25 w / w to about 40 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 27 w / w to about 37 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 31.04 w / w to about 36.96 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 31.0 w / w to about 37.0 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 31.04 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 31.0 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 31.21 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 31.2 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 33.63 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 33.6 w / w. In some embodiments, the amount of PEG 300 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 36.96 w / w. In some embodiments, the amount of PEG 300 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188 and ethanol is about 37.0 w / w.

[0277] In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 10 w / w% to about 70 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 30 w / w% to about 45 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 32 w / w% to about 45 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 34.50 w / w to about 41.85 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 34.5 w / w to about 41.9 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 34.50 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 34.5 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 41.64 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 41.6 w / w. In some embodiments, the amount of the sodium salt of compound Ia or Ib in a solution containing the sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 41.85 w / w. In some embodiments, the amount of sodium salt of compound Ia or Ib in the solution containing sodium salt of compound Ia or Ib, PEG 300, water, poloxamer 188 and ethanol is about 41.9 w / w.

[0278] In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 0.5 w / w% to about 20 w / w%. In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 0.5 w / w% to about 12 w / w. In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 1 w / w% to about 11 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 3.81 w / w to about 7.61 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 3.81 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 3.8 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 6.28 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 6.3 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 7.58 w / w. In some embodiments, the amount of poloxamer 188 in a solution containing the sodium salt of a compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 7.61 w / w. In some embodiments, the amount of poloxamer 188 in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188 and ethanol is about 7.6 w / w.

[0279] In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 0.1 w / w% to about 10 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 1 w / w% to about 9 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is from about 3 w / w% to about 8 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 5.00 w / w. In some embodiments, the amount of ethanol in the solution containing the sodium salt of the compound of formula Ia or Ib, PEG 300, water, poloxamer 188, and ethanol is about 5.0 w / w.

[0280] In some embodiments, the solution comprises about 10 w / w% to about 40 w / w% water, about 20 w / w% to about 75 w / w% PEG 300, about 10 w / w% to about 70 w / w% sodium salt of a compound of formula Ia or Ib, about 0.5 w / w% to about 20 w / w% poloxamer 188, and about 1 w / w% to about 10 w / w% ethanol. In some embodiments, the solution comprises about 10 w / w% to about 20 w / w% water, about 25 w / w% to about 40 w / w% PEG 300, about 30 w / w% to about 45 w / w% sodium salt of a compound of formula Ia or Ib, about 1 w / w% to about 11 w / w% poloxamer 188, and about 3 w / w% to about 8 w / w% ethanol.

[0281] In some embodiments, the solution comprises about 17.26 w / w% water, about 36.96 w / w% PEG 300, about 34.50 w / w% sodium salt of a compound of formula Ia or Ib, about 6.28 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 17.3 w / w% water, about 37.0 w / w% PEG 300, about 34.5 w / w% sodium salt of a compound of formula Ia or Ib, about 6.3 w / w% poloxamer 188, and about 5.0 w / w% ethanol. In some embodiments, the solution comprises about 17.26 w / w% water, about 36.96 w / w% PEG 300, about 34.50 w / w% sodium salt of the compound of formula Ib, about 6.28 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 17.3 w / w% water, about 37.0 w / w% PEG 300, about 34.5 w / w% sodium salt of the compound of formula Ib, about 6.3 w / w% poloxamer 188, and about 5.0 w / w% ethanol.

[0282] In some embodiments, the solution comprises about 15.71 w / w% water, about 33.63 w / w% PEG 300, about 41.85 w / w% sodium salt of a compound of formula Ia or Ib, about 3.81 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 15.7 w / w% water, about 33.6 w / w% PEG 300, about 41.9 w / w% sodium salt of a compound of formula Ia or Ib, about 3.8 w / w% poloxamer 188, and about 5.0 w / w% ethanol. In some embodiments, the solution comprises about 15.71 w / w% water, about 33.63 w / w% PEG 300, about 41.85 w / w% sodium salt of the compound of formula Ib, about 3.81 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 15.7 w / w% water, about 33.6 w / w% PEG 300, about 41.9 w / w% sodium salt of the compound of formula Ib, about 3.8 w / w% poloxamer 188, and about 5.0 w / w% ethanol.

[0283] In some embodiments, the solution comprises about 14.57 w / w% water, about 31.21 w / w% PEG 300, about 41.64 w / w% sodium salt of a compound of formula Ia or Ib, about 7.58 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 14.6 w / w% water, about 31.2 w / w% PEG 300, about 41.6 w / w% sodium salt of a compound of formula Ia or Ib, about 7.6 w / w% poloxamer 188, and about 5.0 w / w% ethanol. In some embodiments, the solution comprises about 14.57 w / w% water, about 31.21 w / w% PEG 300, about 41.64 w / w% sodium salt of the compound of formula Ib, about 7.58 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 14.6 w / w% water, about 31.2 w / w% PEG 300, about 41.6 w / w% sodium salt of the compound of formula Ib, about 7.6 w / w% poloxamer 188, and about 5.0 w / w% ethanol.

[0284] In some embodiments, the solution comprises about 14.50 w / w% water, about 31.04 w / w% PEG 300, about 41.85 w / w% sodium salt of a compound of formula Ia or Ib, about 7.61 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 14.5 w / w% water, about 31.0 w / w% PEG 300, about 41.9 w / w% sodium salt of a compound of formula Ia or Ib, about 7.6 w / w% poloxamer 188, and about 5.0 w / w% ethanol. In some embodiments, the solution comprises about 14.50 w / w% water, about 31.04 w / w% PEG 300, about 41.85 w / w% sodium salt of the compound of formula Ib, about 7.61 w / w% poloxamer 188, and about 5.00 w / w% ethanol. In some embodiments, the solution comprises about 14.5 w / w% water, about 31.0 w / w% PEG 300, about 41.9 w / w% sodium salt of the compound of formula Ib, about 7.6 w / w% poloxamer 188, and about 5.0 w / w% ethanol.

[0285] In some embodiments of the methods described herein, a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, is administered as a parenteral formulation (e.g., for SC or IM administration), which is an aqueous suspension. In some embodiments, the parenteral formulation (e.g., SC or IM formulation) is an aqueous suspension comprising a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, and a saline solution. In some embodiments, the parenteral formulation (e.g., SC or IM formulation) is an aqueous suspension comprising a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, a saline solution, and a suspending agent. In some embodiments, the parenteral formulation (e.g., SC or IM formulation) is an aqueous suspension comprising a compound of formula Ia or Ib, or a pharmaceutically acceptable salt thereof, a saline solution, and poloxamer (such as poloxamer 338, 188, or 207).

[0286] In some embodiments, a suspension comprising poloxamer and a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof in a saline solution is provided. In some embodiments, the concentration of poloxamer in the saline solution is from about 0.1% to about 20%. In some embodiments, the concentration of poloxamer in the saline solution is from about 0.1% to about 10%. In some embodiments, the concentration of poloxamer in the saline solution is from about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%. In some embodiments, the concentration of poloxamer in the saline solution is about 2%. In some embodiments, the poloxamer is poloxamer 188. In some embodiments, the compound is a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of formula Ia. In some embodiments, the compound is a sodium salt of a compound of formula Ia. In some embodiments, the compound is a compound of formula Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of formula Ib. In some embodiments, the compound is a sodium salt of a compound of formula Ib.

[0287] In some embodiments, a suspension comprising poloxamer and a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof in mannitol is provided. In some embodiments, the concentration of poloxamer in mannitol is from about 0.1% to about 20%. In some embodiments, the concentration of poloxamer in mannitol is from about 0.1% to about 10%. In some embodiments, the concentration of poloxamer in mannitol is about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%. In some embodiments, the concentration of poloxamer in mannitol is about 2%. In some embodiments, poloxamer is poloxamer 188. In some embodiments, the compound is a compound of formula Ia or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of formula Ia. In some embodiments, the compound is a sodium salt of a compound of formula Ia. In some embodiments, the compound is a compound of formula Ib or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of formula Ib. In some embodiments, the compound is a sodium salt of a compound of formula Ib.

[0288] In some embodiments, the composition is formulated as a solid dosage form. In some embodiments, the solid dosage form is a solid injectable dosage form, such as a solid reservoir form.

[0289] In some embodiments, the active ingredient (e.g., a compound of formula Ia or Ib) is present as a free acid. In some embodiments, the active ingredient (e.g., a compound of formula Ia or Ib) is present as a sodium salt. In some embodiments, the active ingredient is a compound of formula Ia. In some embodiments, the active ingredient is a compound of formula Ib.

[0290] In some embodiments, the pharmaceutical composition is a parenteral formulation. In some embodiments, the formulation is administered subcutaneously to a patient in need. In some embodiments, the formulation is administered intramuscularly to a patient in need.

[0291] In some embodiments, the parenteral preparation comprises N-methyl-2-pyrrolidone (NMP). In some embodiments, the parenteral preparation consists essentially of N-methyl-2-pyrrolidone. In some embodiments, the parenteral preparation comprises dimethyl sulfoxide (DMSO). In some embodiments, the parenteral preparation comprises polyethylene glycol (PEG) or tetrahydrofuran polyethylene glycol ether. In some embodiments, the solution comprises PEG 200, ethanol, and water. In some embodiments, the solution comprises PEG 300 and water. In some embodiments, the solution comprises poloxamer in saline. In some embodiments, the solution comprises 2% poloxamer 188 in physiological saline.

[0292] In some embodiments, the parenteral preparation comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof and water. In some embodiments, the parenteral preparation comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof and water. In some embodiments, the parenteral preparation comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof and water. In some embodiments, the parenteral preparation also contains an alcohol. In some embodiments, the alcohol is ethanol. In some embodiments, the parenteral preparation also contains polyethylene glycol. In some embodiments, the polyethylene glycol has an average molecular weight of about 200 g / mol (e.g., polyethylene glycol 200). In some embodiments, the parenteral preparation also contains an inorganic base. In some embodiments, the inorganic base is sodium hydroxide (NaOH). In some embodiments, the inorganic base is sodium ethoxide (NaOEt). In some embodiments, the preparation comprises about 0.1 molar equivalents to about 1.5 molar equivalents of an inorganic base. In some embodiments, the preparation comprises about 0.5 molar equivalents to about 1.5 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 0.75 molar equivalents to about 1.2 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.0 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.2 molar equivalents of an inorganic base. In some embodiments, the inorganic base is NaOH or NaOEt.

[0293] In some embodiments, the parenteral formulation comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, water, and polyethylene glycol PEG 300. In some embodiments, the parenteral formulation comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, water, and polyethylene glycol PEG 300.

[0294] In some embodiments, the parenteral formulation comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, water, polyethylene glycol (PEG) 300 (polyethylene glycol with an average molecular weight of 300 g / mol), and NaOH. In some embodiments, the parenteral formulation comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, water, polyethylene glycol (PEG) 300, and NaOEt. In some embodiments, the formulation comprises about 0.1 mol equivalents to about 1.5 mol equivalents of NaOH or NaOEt. In some embodiments, the formulation comprises about 0.5 mol equivalents to about 1.5 mol equivalents of NaOH or NaOEt. In some embodiments, the formulation comprises about 0.75 mol equivalents to about 1.2 mol equivalents of NaOH or NaOEt. In some embodiments, the formulation comprises about 1.0 mol equivalents of NaOH or NaOEt. In some embodiments, the formulation comprises about 1.2 mol equivalents of NaOH or NaOEt.

[0295] In some embodiments, the parenteral formulation is a solution comprising a mixture of ethanol, water, and polyethylene glycol. In some embodiments, the parenteral formulation is a solution comprising a mixture of ethanol, water, and PEG 200. In some embodiments, the solution comprises about 5% to about 20% ethanol, about 5% to about 20% water, and about 60% to about 90% PEG 200. In some embodiments, the solution comprises about 10% to about 15% ethanol, about 10% to about 15% water, and about 70% to about 80% PEG 200. In some embodiments, the solution comprises about 10% ethanol, about 12% water, and about 78% PEG 200. In some embodiments, the solution further comprises an inorganic base. In some embodiments, the solution comprises about 10% ethanol, about 13% water, and about 77% PEG 200. In some embodiments, the solution further comprises an inorganic base. In some embodiments, the formulation comprises about 0.1 molar equivalents to about 1.5 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 0.5 molar equivalents to about 1.5 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.0 molar equivalents to about 1.2 molar equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.2 molar equivalents of an inorganic base. In some embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In some embodiments, the inorganic base is sodium hydroxide.

[0296] In some embodiments, the parenteral formulation is a solution comprising a mixture of water and polyethylene glycol. In some embodiments, the parenteral formulation is a solution comprising a mixture of water and PEG 300. In some embodiments, the solution comprises about 5% w / w to about 25% w / w water and about 75% w / w to about 95% w / w PEG 300. In some embodiments, the solution also comprises an inorganic base. In some embodiments, the formulation comprises about 0.1 mol equivalent to about 1.5 mol equivalents of an inorganic base. In some embodiments, the formulation comprises about 0.5 mol equivalents to about 1.5 mol equivalents of an inorganic base. In some embodiments, the formulation comprises about 0.75 mol equivalents to about 1.2 mol equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.0 mol equivalents of an inorganic base. In some embodiments, the formulation comprises about 1.2 mol equivalents of an inorganic base. In some embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In some embodiments, the inorganic base is sodium hydroxide.

[0297] In some embodiments, the solution comprises a compound of formula Ia or Ib or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solution comprises a compound of formula Ia or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solution comprises a compound of formula Ib or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solution comprises a compound of formula Ia, PEG 300, sodium hydroxide, and water. In some embodiments, the solution comprises a sodium salt of a compound of formula Ib, PEG 300, sodium hydroxide, and water.

[0298] In some embodiments, the solution comprises a compound of formula Ia or Ib, PEG 300, sodium hydroxide, and water. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, sodium hydroxide, and water is from about 50 mg / ml to about 600 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, sodium hydroxide, and water is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, sodium hydroxide, and water is from about 50 mg / ml to about 400 mg / ml. In some embodiments, the concentration of the compound of formula Ia or Ib in the solution comprising the compound of formula Ia or Ib, PEG 300, sodium hydroxide, and water is from about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is from about 75 mg / ml to about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 50 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 75 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 100 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 125 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 150 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 175 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 200 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 225 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 250 mg / ml.In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 275 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about 300 mg / ml. In some embodiments, the concentration of compound Ia or Ib in a solution containing compound Ia or Ib, PEG 300, sodium hydroxide, and water is about...

Claims

1. A method for treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a first time period; (ii) administering to the patient one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a second time period, wherein the second time period occurs after the first time period; and If the patient misses a maintenance dose during the second time period and more than approximately 28 weeks have passed since the previous maintenance dose was administered, the method further includes re-administering the starting dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

2. The method according to claim 1, wherein the first time period is two days.

3. The method of claim 2, wherein the initial dose comprises: On the first day, the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 309 mg / mL, and about 500 mg to about 700 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered orally. as well as On the second day, administer orally about 500 mg to about 700 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof.

4. The method of claim 3, wherein on the first day, the subcutaneous administration is performed by two subcutaneous injections of approximately 309 mg / mL.

5. The method according to claim 3 or 4, wherein on the first day and the second day, the oral administration is administered in the form of two tablets, each tablet containing about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

6. The method according to claim 3 or 4, wherein on the first day and the second day, the oral administration is administered in the form of two tablets, each tablet containing about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof.

7. The method of claim 2 or 3, wherein the initial dose comprises: On the first day, 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered subcutaneously, and about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. as well as On the second day, approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered orally.

8. The method according to claim 1, wherein the first time period is fifteen days.

9. The method of claim 8, wherein the initial dose comprises: On the first day and the second day, about 500 mg to about 700 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, administer orally about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; as well as On day 15, the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of approximately 309 mg / mL.

10. The method of claim 9, wherein the oral administration is administered in the following manner: two tablets on the first day and the second day, each tablet containing about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and one tablet on the eighth day, the tablet containing about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

11. The method according to claim 9 or 10, wherein the oral administration is administered in the following manner: two tablets on the first day and the second day, each tablet containing about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and one tablet on the eighth day, the tablet containing about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

12. The method according to any one of claims 9 to 11, wherein on the fifteenth day, the subcutaneous administration is performed by two subcutaneous injections of approximately 309 mg / mL.

13. The method of claim 8 or 9, wherein the initial dose comprises: On the first and second days, approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. as well as On the fifteenth day, 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered subcutaneously.

14. A method of treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first day and the second day, oral administration of about 500 mg to about 700 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; (b) On the eighth day, oral administration of about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and (c) On the fifteenth day, administer subcutaneously a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, followed by the initial dose used in steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as early as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further includes administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or When the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further includes, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof. as well as (ii) Administering one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a second time period, wherein the second time period occurs after the first time period.

15. The method of claim 14, wherein the oral administration is administered in the following manner: two tablets on the first day and the second day, each tablet containing about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and one tablet on the eighth day, the tablet containing about 200 mg to about 400 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

16. The method of claim 14, wherein the oral administration is administered in the following manner: two tablets on the first day and the second day, each tablet containing about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and one tablet on the eighth day, the tablet containing about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

17. The method according to any one of claims 14 to 16, wherein on the fifteenth day, the subcutaneous administration is performed by two subcutaneous injections of approximately 309 mg / mL.

18. The method of claim 14, wherein the initial dose comprises: On the first and second days, approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. On the eighth day, approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. as well as On the fifteenth day, 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered subcutaneously.

19. The method according to any one of claims 14 to 18, wherein when the patient misses the oral administration on the second day and the oral administration is missed for less than six days, the method further comprises administering to the patient about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof as early as possible after the missed dose, and subsequently completing the initial dose of steps (b) and (c).

20. The method according to any one of claims 14 to 18, wherein when the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further comprises administering to the patient as early as possible after the missed dose about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, on the fifteenth day, administering orally about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, administering subcutaneously 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof.

21. The method according to any one of claims 14 to 18, wherein when the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further comprises administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day.

22. The method according to any one of claims 14 to 18, wherein when the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further comprises administering to the patient as early as possible after the missed dose about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day.

23. The method according to any one of claims 14 to 18, wherein when the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further comprises, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof.

24. The method according to any one of claims 3 to 7, wherein the second time period begins approximately 26 weeks after the final oral administration of the initial dose.

25. The method according to any one of claims 9 to 23, wherein the second time period begins approximately 26 weeks after the final subcutaneous administration of the initial dose.

26. The method according to any one of claims 1 to 25, wherein each maintenance dose comprises subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks.

27. The method according to any one of claims 1 to 26, wherein each maintenance dose comprises two subcutaneous injections of about 309 mg / mL every 26 weeks.

28. The method according to any one of claims 1 to 27, wherein each maintenance dose comprises subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof every 26 weeks.

29. A method of treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose to the patient, the initial dose comprising, on the first day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and oral administration of about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof; as well as On the second day, approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered orally. (ii) Administer one or more maintenance doses to the patient, each maintenance dose comprising subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks; Maintenance dose administration begins approximately 26 weeks after the final oral administration of the initial dose; and Where the patient misses a maintenance dose and more than approximately 28 weeks have passed since the previous maintenance dose was administered, the method further includes re-administering the starting dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

30. A method of treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering an initial dose to the patient, the initial dose comprising, on the first and second days, an oral administration of about 600 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; On the eighth day, approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. as well as On the fifteenth day, 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof was administered subcutaneously. (ii) Administering a maintenance dose to the patient, the maintenance dose comprising subcutaneous administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof at a concentration of about 309 mg / mL every 26 weeks; The maintenance dose is administered approximately 26 weeks after the final subcutaneous administration of the initial dose; and Where the patient misses a maintenance dose and more than approximately 28 weeks have passed since the previous maintenance dose was administered, the method further includes re-administering the starting dose of step (i) to the patient before restarting the administration of one or more maintenance doses of step (ii).

31. A method of treating or preventing HIV in a patient, the method comprising administering a compound of formula Ia to the patient: Ia Or a pharmaceutically acceptable salt thereof, the method comprising: (i) Administering to the patient an initial dose of a compound of formula Ia or a pharmaceutically acceptable salt thereof for a first time period of fifteen days, the initial dose comprising: (a) On the first and second days thereafter, about 600 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof was administered orally. (b) On the eighth day, administer orally about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof; and (c) On the fifteenth day, administer 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously; in: If the patient misses the oral administration on the second day and the missed oral administration is less than six days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as early as possible after the missed dose, followed by the initial dose used in steps (b) and (c); or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering approximately 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as early as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the second day and the oral administration is missed for six or more days, the method further includes administering about 600 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient on the eighth day, administering about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or If the patient misses the oral administration on the eighth day and the oral administration is missed for less than six days, the method further includes administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient as soon as possible after the missed dose, administering approximately 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof orally on the fifteenth day, and administering 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof subcutaneously on the fifteenth day; or When the patient misses the oral administration on the eighth day and the oral administration is missed for six or more days, the method further includes, on the fifteenth day, oral administration of about 300 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof, and on the fifteenth day, subcutaneous administration of 927 mg of the compound of formula Ia or a pharmaceutically acceptable salt thereof. as well as (ii) Administering one or more maintenance doses of a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient for a second time period, wherein the second time period occurs after the first time period.

32. The method according to any one of claims 1 to 31, wherein the compound of formula Ia is applied as a sodium salt.

33. The method according to any one of claims 1 to 32, wherein each subcutaneous application is administered with a solution comprising a sodium salt of a compound of formula Ia.

34. The method of claim 33, wherein each solution comprises about 20 w / w% to about 30 w / w% water, about 48 w / w% to about 60 w / w% PEG 300 and about 11 w / w% to about 28 w / w% sodium salt of the compound of formula Ia.

35. The method according to claim 33 or 34, wherein each solution comprises about 23.41 w / w% water, about 50.13 w / w% PEG 300 and about 26.46% sodium salt of the compound of formula Ia.

36. The method of claim 33, wherein each solution comprises about 309 mg / mL of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

37. The method of claim 33, wherein each solution comprises about 315.4 mg / mL of a sodium salt of the compound of formula Ia.

38. The method according to any one of claims 1 to 37, wherein each oral administration is administered as a tablet comprising a sodium salt of a compound of formula Ia.

39. The method of claim 38, wherein each tablet is prepared by spray drying dispersion technology.

40. The method of claim 38 or 39, wherein each tablet comprises about 5 w / w% to about 45 w / w% of the sodium salt of the compound of formula Ia, about 1 w / w% to about 10 w / w% of copovidone, about 0.01 w / w% to about 10 w / w% of poloxamer 407, about 5 w / w% to about 45 w / w% of microcrystalline cellulose, about 15 w / w% to about 70 w / w% of mannitol, about 1 w / w% to about 30 w / w% of croscarmellose sodium, and about 0.01 w / w% to about 10 w / w% of magnesium stearate, and one or more pharmaceutically acceptable excipients.

41. The method according to claim 38 or 39, wherein each tablet comprises about 15 w / w% to about 25 w / w% of the sodium salt of the compound of formula Ia, about 3 w / w% to about 6 w / w% of copovidone, about 0.5 w / w% to about 3.0 w / w% of poloxamer 407, about 18 w / w% to about 30 w / w% of microcrystalline cellulose, about 40 w / w% to about 50 w / w% of mannitol, about 6 w / w% to about 10 w / w% of croscarmellose sodium, and about 1.0 w / w% to about 3.0 w / w% of magnesium stearate.

42. The method according to any one of claims 38 to 41, wherein each tablet contains about 300 mg of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

43. The method according to any one of claims 38 to 41, wherein each tablet contains about 306.8 mg of the sodium salt of the compound of formula Ia.

44. The method according to any one of claims 38 to 43, wherein each tablet further comprises an outer film coating.

45. The method of claim 44, wherein the outer film coating provides a weight gain of about 1% to about 8% based on the uncoated tablet.

46. ​​The method of claim 44, wherein the outer film coating provides approximately 4% weight gain based on the uncoated tablet.

47. The method according to any one of claims 1 to 46, wherein the method is a method for preventing human immunodeficiency virus (HIV) infection in the patient.

48. The method according to any one of claims 1 to 47, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered as a monotherapy.

49. The method according to any one of claims 1 to 48, wherein the method comprises administering a compound of formula Ia or a pharmaceutically acceptable salt thereof to the patient in an event-driven manner.

50. The method according to any one of claims 1 to 49, wherein the method comprises pre-exposure prophylaxis (PrEP).

51. The method according to any one of claims 1 to 49, wherein the method includes post-exposure prophylaxis (PEP).

52. The method according to any one of claims 1 to 49, wherein the method comprises pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).

53. The method according to any one of claims 1 to 50, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered to the patient prior to exposure to the HIV.

54. The method according to any one of claims 1 to 50, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered once daily for about 14 days to about once daily before the patient is exposed to the HIV.

55. The method according to any one of claims 1 to 50, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered once approximately 10 days to approximately 5 days before the patient is exposed to the HIV.

56. The method according to any one of claims 1 to 50, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered once approximately 7 days before the patient is exposed to the HIV.

57. The method according to any one of claims 1 to 50, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered once approximately 72 hours to approximately 1 hour before the patient is exposed to the HIV.

58. The method of claim 50 or 52, wherein the pre-exposure prophylaxis (PrEP) comprises continuous PrEP.

59. The method according to any one of claims 1 to 58, the method comprising administering a compound of formula Ia or a pharmaceutically acceptable salt thereof during the period during which the patient is exposed to the HIV.

60. The method according to any one of claims 1 to 59, the method comprising administering a compound of formula Ia or a pharmaceutically acceptable salt thereof after the patient has been finally exposed to the HIV.

61. The method according to any one of claims 1 to 60, wherein the patient is a patient who has undergone intensive treatment.

62. The method of claim 61, wherein the HIV infection is characterized by HIV-1 infection with resistance to one or more antiretroviral drugs in an HIV-1 mutant.

63. The method of claim 61, wherein the HIV infection is characterized by HIV-1 infection with resistance to two or more antiretroviral drugs in an HIV-1 mutant.

64. The method of claim 61, wherein the HIV infection is characterized by HIV-1 infection with resistance to three or more antiretroviral drugs in an HIV-1 mutant.

65. The method according to any one of claims 61 to 64, wherein the HIV-1 mutant is resistant to protease inhibitors (PI), nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTI), or integrase strand transfer inhibitors (INSTI).

66. The method of claim 65, wherein the HIV-1 mutant resistant to protease inhibitors is selected from I50V, I84V / L90M, G48V / V82A / L90M, and G48V / V82S.

67. The method of claim 65, wherein the HIV-1 mutant resistant to nucleoside or nucleotide reverse transcriptase inhibitors is selected from K65R, M184V, and 6TAM.

68. The method of claim 65, wherein the HIV-1 mutant resistant to non-nucleoside or non-nucleotide reverse transcriptase inhibitors is selected from K103N, Y181C, Y188L, L100I / K103N, and K103N / Y181C.

69. The method of claim 65, wherein the HIV-1 mutant resistant to integrase strand transfer inhibitors is selected from Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I.

70. The method according to any one of claims 61 to 69, wherein the patient is infected with HIV-1 that is resistant to at least one antiretroviral drug.

71. The method according to any one of claims 61 to 70, wherein the patient is infected with multidrug-resistant HIV-1, the multidrug-resistant HIV-1 being resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

72. The method according to any one of claims 61 to 70, wherein the patient is infected with multidrug-resistant HIV-1, the multidrug-resistant HIV-1 being resistant to at least one antiretroviral drug from each of three different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

73. The method according to claim 71 or 72, wherein the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI).

74. The method according to any one of claims 65 to 73, wherein the NRTI is selected from emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), doxorinosine (ddI), dideoxyinosine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (deoxycytidine, ddC), and abacavir.

75. The method according to any one of claims 65 to 74, wherein the NNRTI is selected from efavirenz, ectavirin, rilpivirine, nevirapine, and delavudine.

76. The method according to any one of claims 65 to 75, wherein the PI is selected from ampravir, atazanavir, drenavirvir, fosanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and telanavir.

77. The method according to any one of claims 65 to 76, wherein the INSTI is selected from Retegwer, Ertiravir, Durutvir, Cabotevir, and Bicagwer.

78. The method according to any one of claims 61 to 77, wherein the patient has previously been treated with at least one antiretroviral drug for at least 3 months.

79. The method according to any one of claims 61 to 77, wherein the patient has previously been treated with at least one antiretroviral drug for at least 6 months.

80. The method according to any one of claims 61 to 77, wherein the patient has previously been treated with at least one antiretroviral drug for at least 9 months.

81. The method according to any one of claims 61 to 77, wherein the patient has previously been treated with at least one antiretroviral drug for at least 12 months.

82. The method according to any one of claims 61 to 81, wherein the patient has not undergone a prior HIV treatment regimen that includes administration of at least one antiretroviral drug.

83. The method according to any one of claims 78 to 82, wherein the prior treatment regimen comprises administering at least one antiretroviral drug from each of two different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

84. The method according to any one of claims 78 to 82, wherein the prior treatment regimen comprises administering at least one antiretroviral drug from each of three different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

85. The method according to claim 83 or 84, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).

86. The method according to any one of claims 1 to 85, wherein the patient has not undergone an HIV treatment regimen comprising the administration of at least one antiretroviral drug when initiating administration of a compound of formula Ia or a pharmaceutically acceptable salt thereof.

87. The method according to any one of claims 1 to 86, wherein administration of the compound of formula Ia or a pharmaceutically acceptable salt thereof results in a reduction of viral load in the patient.

88. The method according to any one of claims 1 to 47 and 49 to 87, wherein the method further comprises administering one, two, three or four additional therapeutic agents to the patient.

89. The method of claim 88, wherein the additional therapeutic agent is selected from the group consisting of: combination drugs for HIV, other drugs for treating HIV, HIV protease inhibitors, non-nucleoside or non-nucleotide inhibitors of HIV reverse transcriptase, nucleoside or nucleotide inhibitors of HIV reverse transcriptase, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, HIV entry inhibitors, HIV maturation inhibitors, latency reversal agents, compounds targeting the HIV capsid, immunotherapy, phosphatidylinositol 3-kinase (PI3K) inhibitors, HIV antibodies, bispecific antibodies and "antibody-like" therapeutic proteins, HIV p17 matrix protein inhibitors, IL-13 antagonists, peptidyl prolyl cis-trans isomerase A modulators, protein disulfide isomerase inhibitors, complement C5a receptor antagonists, DNA methyltransferase inhibitors, HIV vif gene modulators, Vif dimerization antagonists, HIV-1 viral infectious agent inhibitors, TAT protein inhibitors, HIV-1 Nef modulators, Hck tyrosine kinase modulators, mixed lineage kinase-3 (MLK-3) inhibitors, HIV-1 splicing inhibitors, Rev protein inhibitors, integrin antagonists, nucleoprotein inhibitors, splicing factor modulators, protein 1 modulators containing the COMM domain, HIV ribonuclease H inhibitors, retrocyclin modulators, CDK-9 inhibitors, dendritic cell ICAM-3 non-integrin 1 inhibitors, HIV GAG protein inhibitors, HIV POL protein inhibitors, complement factor H modulators, ubiquitin ligase inhibitors, deoxycytidine kinase inhibitors, cyclin-dependent kinase inhibitors, proprotein convertase PC9 stimulators, ATP-dependent RNA helicase DDX3X inhibitors, reverse transcriptase initiation complex inhibitors, G6PD and NADH-oxidase inhibitors, pharmacokinetic enhancers, HIV gene therapy and HIV vaccines, or any combination thereof.

90. The method of claim 88 or 89, wherein the additional therapeutic agent is selected from the group consisting of: HIV protease inhibitory compounds, non-nucleoside inhibitors of HIV reverse transcriptase, non-nucleotide inhibitors of HIV reverse transcriptase, nucleoside inhibitors of HIV reverse transcriptase, nucleotide inhibitors of HIV reverse transcriptase, HIV integrase inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, pharmacokinetic enhancers, and other drugs for the treatment of HIV or any combination thereof.

91. The method according to any one of claims 88 to 90, wherein the additional therapeutic agent is selected from the group consisting of: bicagvir or a pharmaceutically acceptable salt thereof, abacavir sulfate, tenofovir, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate, tenofovir alafenamide, and tenofovir alafenamide fumarate.

92. The method according to any one of claims 88 to 91, wherein the additional therapeutic agent is selected from the group consisting of: bicagvir or a pharmaceutically acceptable salt thereof, tenofovir alafenamide, tenofovir alafenamide fumarate, and tenofovir alafenamide hemifumarate.

93. The method according to any one of claims 88 to 92, wherein the additional therapeutic agent is administered simultaneously with a compound of formula Ia or a pharmaceutically acceptable salt thereof.

94. The method according to any one of claims 88 to 93, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is combined with the additional therapeutic agent in a single dosage form for simultaneous administration.

95. The method according to any one of claims 88 to 93, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is administered sequentially with the additional therapeutic agent.

96. The method according to any one of claims 1 to 95, wherein the compound of formula Ia or a pharmaceutically acceptable salt thereof is a compound of formula Ib: Ib Or its pharmaceutically acceptable salt.

97. The method of claim 96, wherein the compound of formula Ib is administered as a sodium salt.

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