Antiviral treatments

Inactive Publication Date: 2007-08-30
BIOCRYST PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0003] It has unexpectedly been discovered that a single intravenous administration of peramivir to a mouse is effective to treat influenza. These findings are unexpected not only because of the high effectiveness of a single administration of the compound, but also because of the low dose of the compound that was found to provide effective treatment. The ability to obtain therapeutically useful effects with a single administration is important inter alia because it minimizes patient compliance issues resulting from the need for multiple administrations. Additionally, the administration of a low dose is important because it minimizes cost and the potential for side-effects. It has also been unexpectedly discovered that intravenous and intramuscular injections of peramivir to humans provides high plasma concentrations of peramivir with an extended half-life.
[0009] The invention also provides the use of a compound of formula I, II, III, or IV, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for intravenous injection for increasing life expectancy or reducing mortality in a group of mammals exposed to a source of an influenza virus, by intravenous injection of a dose of the medicament into each member of the group presenting clinical symptoms of infection.
[0010] The invention also provides the use of a compound of formula I, II, III, or IV, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for intravenous injection for increasing life expectancy or reducing mortality in a group of mammals exposed to a source of an influenza virus, by intravenous injection of a dose of the medicament into each member of the group.

Problems solved by technology

Unfortunately, clinical trials using this drug showed a suboptimal therapeutic effect on influenza infection in humans following oral administration over a period of days.

Method used

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  • Antiviral treatments
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Examples

Experimental program
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Effect test

example 1

Effect of IV Treatment with Peramivir on Influenza a Virus Infection

[0099] Experiment Design: Mice were infected i.n. with a dose thought to be the LD100 of influenza virus. Groups of 10 mice were treated i.v. with peramivir at dosages of 20, 10 and 3 mg / kg a single time 1 hour pre-virus exposure. Placebo (sterile saline) was administered i.v. in parallel with the above to 20 infected mice. Drug-treated infected mice and placebo-treated controls were observed daily for death through 21 days. As toxicity controls, 3 uninfected mice were treated with the highest dose of the compounds in parallel to the infected animals. All toxicity controls were observed for death through 21 days and were weighed immediately prior to the initial treatment and 18 h after the final treatment. Five normal controls were weighed.

TABLE 2Effect of Single I.V. Treatment with Peramivir on an Influenza A VirusInfection in Mice.Animals: Female 18-21 gramTreatment schedule: Peramivir,: SingleBALB / c micetreatm...

example 2

Effects of IV and IM Treatment with Peramivir in Humans

[0101] Peramivir was studied in a placebo-controlled phase I clinical study in healthy human volunteers to evaluate safety and pharmacokinetic parameters using intravenous and intramuscular administrations. Blood samples were collected from the subjects at different time points after drug administration to determine the concentration of the drug in plasma. The time course plots are shown in FIG. 1 and FIG. 2 for intravenous and intramuscular administrations respectively.

[0102] In the intravenous study, peramivir concentrations followed linear kinetics with an unusually extended plasma half life of greater than 12 hours. At doses of 2 mg / kg and above, the level of peramivir in plasma at 48 hours post-dose is greater than the IC50 for all strains of influenza virus tested, including H5 virus types. For doses greater than 4 mg / kg, even at 72 hours, the levels of the drug are greater than the IC50 values.

[0103] In the intramuscul...

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Abstract

The invention provides unit dosage forms, kits, and methods useful for treating viral infections.

Description

RELATED APPLICATION(S) [0001] This patent document claims the benefit of priority of U.S. application Ser. No. 60 / 772,748, filed Feb. 13, 2006, which application is herein incorporated by reference.BACKGOUND [0002] The influenza virus neuraminidase inhibitor peramivir has marked activity against the influenza virus in vitro and in experimentally infected mice (Govorkova et al., Antimicrobial Agents and Chemotherapy, 45(10), 2723-2732 (2001); and Smee et al., Antimicrobial Agents and Chemotherapy, 45(3), 743-748 (2001)). Unfortunately, clinical trials using this drug showed a suboptimal therapeutic effect on influenza infection in humans following oral administration over a period of days. Currently there is a need for methods and formulations that are useful for treating viral infections (e.g., influenza infections) in humans. SUMMARY OF THE INVENTION [0003] It has unexpectedly been discovered that a single intravenous administration of peramivir to a mouse is effective to treat inf...

Claims

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Application Information

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IPC IPC(8): A61K31/195
CPCA61K31/195A61K9/0019A61K45/06A61K31/196A61K31/215A61K9/006A61P31/12A61P31/16
InventorBABU, YARLAGADDA SUDHAKARACHAND, POORANBANTIA, SHANTAARNOLD, SHANEKILPATRICK, JOHN MICHAEL
OwnerBIOCRYST PHARM INC