System for determining the time and / or the dose of a medicament to be administered to a patient

Abstract

The present invention proposes a system (100) for determining the time and / or the dose of a medicament (AM) to be administered to a patient (P), the system (100) comprising, or consisting of, an electronic control device (9); a data memory (M) for storing at least administration times (tA0, tA1, tA2,..., tA(n- 1)) of one or a plurality of already administered dosage forms of the medicament (DFAM0, DFAM1, DFAM2,..., DFAM(n-1)) and / or the dose (D0, D1, D2,..., D(n-1)) of these already administered dosage forms of the medicament (DFAM0, DFAM1, DFAM2,..., DFAM(n-1)); a feedback device (8) for capturing patient data relating to the patient response to an administration of a dosage form of the medicament (DFAM); wherein the electronic control device (9) is further programmed for reading out data stored in the data memory (M); evaluating the patient data captured by the feedback device (8); and for determining the time (tAn, tA(n+1), tA(n+2),..., tA(n+x)) and / or the dose (Dn, D(n+1), D(n+2),..., D(n+x)) for administering the next or the further dosage form(s) of the medicament (DFAMn, DFAM(n+1), DFAM(n+2),..., DFAM(n+x)) taking into account the read-out and captured data. The system (100) also has an output device, in particular an information output device (17), for outputting information relating to the determined time(s) (tAn, tA(n+1), tA(n+2),..., tA(n+x)) and / or the determined dose (Dn, D(n+1), D(n+2),..., D(n+x)) of the next or further dosage form(s) of the medicament (DFAM), or for outputting the next or further dosage form(s) of the medicament (DFAM).

Description

[0001] Hatchmore Labs GmbH

[0002] System for determining the time and / or dose of a drug to be administered to a patient

[0003] The present invention relates to a system for determining the time and / or dose of a drug to be administered to a patient according to claim 1 or according to the preamble or generic term of this claim.

[0004] Patients are all different. They differ in age, weight, and gender, and / or have complex medical histories. A patient may also have multiple comorbidities and take a wide range of medications. Furthermore, they will have different lifestyles, values, and perspectives. Personalized drug dosing aims to recognize this heterogeneity and enable the optimal dosing regimen to be found for each patient.

[0005] Pharmacological models are used to describe the body's response to the administration of a drug. A pharmacological model is typically divided into two parts: the pharmacokinetic (PK) behavior of a drug, i.e., the relationship between the drug's dosage regimen and the corresponding drug concentration, e.g., in the blood, on the one hand, and the pharmacodynamic (PD) behavior, which quantifies the relationship between the drug's concentration, e.g., in the blood, and its effect. Simply put, pharmacokinetics is what the body does with the drug, and pharmacodynamics is what the drug does to the body.

[0006] Pharmacological modeling, including PK / PD modeling, encompasses a wide range of flexible models to simultaneously describe how both PK and PD change over time, with time-dependent PD changes driven by time-dependent PK changes (although delayed effects may occur depending on the case).

[0007] A key component of pharmaceutical pharmacokinetics (PK) deals with the release, absorption, distribution, metabolism, and excretion of the drug (LADME). These subprocesses play a central role in determining the blood plasma concentrations of the drug observed over time. These drug concentrations can be described at a specific time point (e.g., Ctrough, a "trough" drug concentration measured shortly before successive dosing events) or as the maximum drug concentration (Cmax) or average drug concentration (Cave) over the intradosing interval, i.e., over the interval between two successive dosing events.

[0008] Other key concepts in pharmacokinetics include volume of distribution, accumulation (when drug concentrations in the body increase over time with successive doses), steady state (accumulation ends and drug concentrations reach a dynamic equilibrium with successive doses), dose proportionality (dose linearity) or nonlinearity (regardless of whether the magnitude of the concentrations changes directly with the magnitude of the dose changes or not), bioavailability, and clearance (CL).

[0009] In general, the time-dependent concentration of drugs in blood plasma is very important, as the drug usually reaches its site of action via the bloodstream (exceptions are generally the route of administration, such as inhaled drugs (e.g., for asthma) or topical drugs (e.g., for psoriasis)). Important considerations for pharmacokinetics also include drug interactions (where taking two drugs can alter the pharmacokinetics of one or both drugs) and the role of active metabolites (when the main molecule is metabolized to another molecule that can itself induce a drug effect). Active metabolites of a drug are compounds that are formed when the body metabolizes a drug.These metabolites retain some or all of the pharmacological activity of the original drug or may even play a crucial role in determining the efficacy, tolerability, and safety of a Hatchmore Labs GmbH.

[0010] Drug interactions can play a role. They can enhance the therapeutic effect, prolong the response time, or contribute to side effects and toxicity.

[0011] Pharmacodynamics (PD) deals with the biological effects of a drug on the body, depending on the dose and concentration of the drug, e.g., in the blood and / or at the site of action. These are the body's responses to the drug that are important for the patient. These responses are often referred to as benefit (i.e., efficacy) and harm (i.e., compromises in safety / tolerability) and thus encompass all clinical endpoints measured in clinical trials and / or during real-world treatments.

[0012] A patient's reaction to an administered drug can be classified as either subjective or objective.

[0013] Objective patient responses are based on measurable, qualitative, or quantifiable changes in physiological parameters or biomarkers that can be observed and recorded independently of the patient's perception. These responses are typically assessed using standardized instruments, laboratory tests, or imaging techniques. Examples include changes in blood biomarkers (e.g., C-reactive protein levels), physiological measurements (e.g., blood pressure, heart rate), and quantifiable motor symptoms (e.g., tremor rate measured by devices).

[0014] Subjective patient responses are based on the patient's personal experience, perception, and self-assessment of symptoms or effects. These responses are inherently influenced by individual factors and can vary from patient to patient. Examples include patient-reported pain intensity, self-assessed quality of life (QoL), and perceived symptom improvement.

[0015] Both objective and subjective patient responses can provide valuable information about the efficacy, tolerability, safety, and / or benefit profile of a drug. There are cases in which PD effects occur almost instantaneously with the change in pharmacokinetics (a "direct" effect). However, changes in PD effects usually occur with a delay relative to the pharmacokinetic concentration (an "indirect" effect). For example, the skin of a patient with psoriasis will not change immediately after the first dose but will improve slowly over the course of treatment, over days, weeks, or even months.

[0016] In cases where the delay in response is substantial (e.g., weeks or months), relative to the frequency of the dosing regimen (e.g., daily), it can be useful to correlate a simple measure of drug exposure, such as the average concentration (Cave), with the PD endpoint. However, there are notable exceptions, such as when particularly high concentrations may be more strongly associated with acute toxicity than the average concentration. In this case, Cmax may be more informative than Cave. Generally, multiple PK samples are collected from each patient during drug development, as this allows for the prediction of their complete PK profile over time and thus a much more accurate understanding of the interplay between observed PD effects and the PK effects that drive them.

[0017] Drug treatment utility can be viewed as the overall assessment a patient assigns to their various individual responses to drug therapy. It represents the balance between desired drug effects (benefit) and undesired drug effects (harm). More specifically, drug treatment utility concerns how patients actually evaluate the trade-off between benefits and harms. For example, if an epilepsy patient achieved a 50% reduction in seizures with their initial dose but subsequently experienced 1-4 moderate headaches each month, would they consider this trade-off worthwhile (a positive benefit) or not (a negative benefit)? Furthermore, would they prefer lower or Hatchmore Labs GmbH

[0018] Trying higher doses to discover a better dose for oneself (i.e., a dose with greater individual benefit)?

[0019] In clinical practice, this means finding the individual balance between efficacy, safety and tolerability of a drug therapy.

[0020] Efficacy can be generally defined as the ability of a drug to exert its intended therapeutic effect under ideal conditions, such as in a controlled clinical trial. Efficacy can be measured, for example, by the maximum achievable response (Emax) and is an important parameter in determining the potential therapeutic benefit of a drug. Efficacy can also correlate with, for example, the specific binding constant of the drug or its active metabolite to the pharmacological target, or with the constant for the specific inhibition of the pharmacological target by the drug or its active metabolite.

[0021] Safety can be generally defined as the absence of unacceptable risks or harm when a drug is used as directed. Safety encompasses the evaluation of adverse events, toxicities, and potential long-term effects associated with drug administration.

[0022] Tolerability can be generally defined as the extent to which a patient can tolerate the apparent side effects of a drug. While closely related to safety, tolerability focuses on the patient's own experience and their ability to adhere to a treatment regimen without significant discomfort or disruption to daily activities. For pharmacodynamic considerations, dose-exposure (DE), exposure-response (ER), and dose-exposure-response (DER) relationships are also important, as they describe the complex interactions between drug administration, drug concentration in the body, and the resulting physiological effects.

[0023] The dose-exposure (DE) relationship refers to the relationship between the administered dose of a drug and the resulting concentration of the drug in the body, typically measured in plasma or at the site of action. This relationship can be influenced by various pharmacokinetic factors, including absorption, distribution, metabolism, and excretion. The dose-exposure relationship can be linear or nonlinear, depending on the properties of the drug and the dose range under investigation.

[0024] The exposure-response relationship (ER) refers to the correlation between the concentration of a drug in the body (exposure) and the extent of the observed pharmacological or toxicological effect (response). This relationship is often characterized by exposure-response curves, which illustrate how the intensity or frequency of a biological response changes with increasing drug concentration. The exposure-response relationship can be influenced by factors such as receptor binding, signal transduction, and the development of tolerance.

[0025] Personalized drug dosing, as described herein, aims to determine and qualify or quantify each patient's DER relationships for the drug(s) with which they are treated. The sequence from dose to benefit varies for different patients. By understanding these individual DER relationships, each patient's drug therapy can be guided based on their own individual treatment benefit.

[0026] A major challenge in optimizing individualized drug therapy is the variability of each patient's response to the drug. There are two main types of patient variability that lead to different drug responses. Hatchmore Labs GmbH

[0027] can, and which affect efficacy, safety, tolerability, or a combination thereof.

[0028] Interindividual variability can be described as differences between individual patients resulting from factors such as genetic polymorphisms, variations in receptor density, and disparities in drug metabolism and elimination processes. This variability can lead to significantly different drug effects and responses between patients, even when they receive the same dose.

[0029] Intraindividual variability can be described as time-dependent fluctuations within a single patient and can further complicate individual dose optimization. This includes daily fluctuations in physiological parameters, temporal variations in drug concentrations, and changes in response to the drug, e.g., due to environmental factors or circadian rhythms.

[0030] These variability factors pose challenges for both traditional dosing approaches and more advanced approaches such as therapeutic drug monitoring (TDM). High variability between individual administration events, a form of intraindividual variability, can render measurements at a specific time point unreliable for dose adjustments. Furthermore, the complex interplay between genetic, physiological, and environmental factors influencing drug response limits the predictive power of single-factor approaches such as pharmacogenomics.

[0031] To optimize the individual dose for each patient, it is important to understand and consider that (i) there is interindividual variability between different patients in both pharmacokinetics (PK) and peritoneal diabetic (PD), and (ii) that each patient has their own individual DER relationships for each treatment endpoint. This means that each patient has their own individual dose-exposure (DE) relationship (interindividual variability in PK) and their own individual exposure-response (ER) relationship (interindividual variability in PD).

[0032] Therefore, administering a fixed dosage regimen to a group of patients leads to a wide range of "exposures" (drug concentrations, e.g., caution), and the responses to these drug concentrations also differ between patients. A fixed dosage regimen can be considered an "optimal" compromise for a uniform dose for the entire patient population, but will lead to suboptimal responses or treatment outcomes in many individual patients.

[0033] One solution may be to offer a group of patients (fixed) dosage options within a wider range to achieve the same exposure (e.g., the dose is adjusted or "titrated" to achieve a specific exposure). A wide range of dosage options is needed here to achieve the same exposure across different patients (due to interindividual variability in pharmacokinetics). Nevertheless, a uniform level of drug exposure within a patient population will lead to inconsistent patient responses (due to interindividual variability in pharmacokinetics). Therapeutic drug monitoring (TDM) may be an approach to finding the "optimal" exposure for an individual patient.However, TDM and similar approaches link individual exposure to exposure-response relationships (ERs) determined at the population level, which do not reflect the ER relationship of the individual patient (interindividual variability in PD).

[0034] In summary, administering the same dosage forms with a uniform dosing regimen to all patients leads to a wide range of individual patient responses, whereas achieving at least a similar patient response in all patients would require a wide range of individualized dosage forms and / or individualized dosing regimens. Enabling patients to achieve the individually optimal treatment outcome with a drug therapy would be a desirable step towards personalized medicine. Hatchmore Labs GmbH

[0035] As previously mentioned, patients differ in several aspects, including genetics, ethnicity, sex, age, weight, comorbidities, concomitant medications, diet, and other factors, all of which can influence the efficacy and success of drug therapy for each individual patient. This makes patient-specific drug therapy a significant and often technically challenging undertaking. While physicians practice evidence-based medicine, they often have limited resources or access to only one or a few dosage strengths approved for a theoretical, "average" patient. Such so-called "population-based doses" often lead to a "one-size-fits-all" approach and thus to a suboptimal dosing regimen.

[0036] The object of the present invention is to propose a system for determining the time and / or dose of a drug to be administered to a patient.

[0037] The problem according to the invention can be solved by the system with the features of claim 1.

[0038] The invention, as described herein, is a (modular) personalized dosing system for determining (and optionally dispensing) a, preferably the best, dosage regimen for each individual patient by means of dose calculation, controlled by specifically monitored variables during treatment for efficacy, safety, tolerability (or any combination thereof). It is based on any combination of the following points:

[0039] The system can determine a dosage regimen, preferably the best one, based on the individual characteristics of the patient; and / or

[0040] The system can determine whether the initial dosing regimen needs to be changed for efficacy, safety, and / or tolerability reasons, how best to accomplish this, and / or select the optimal dosing algorithm. This process may use, but is not limited to, data such as clinical trial endpoints, biomarkers, diagnostics, and / or patient-reported outcomes (PROs) to determine (i) when the dose should be changed and (ii) by how much; and / or

[0041] The system can be used to determine the circumstances under which treatment must be discontinued. This could be the case, for example, if no dose can be found for the patient whose benefit-risk ratio is sufficiently positive to justify continuing the dosage.

[0042] The system discussed herein is the subject of the present invention and is therefore in accordance with the invention.

[0043] The present invention therefore provides a system of functional components that makes it possible to individually optimize the dose and / or dosage regimen for each individual patient by capturing quantitative and / or qualitative patient feedback and taking it into account by dosage algorithms also described herein.

[0044] In all the preceding and following statements, the use of the expression "may be" or "may have" etc. is to be understood as synonymous with "is preferably" or "has preferably" etc. and is intended to explain an embodiment according to the invention.

[0045] Whenever numerical terms are used herein, a person skilled in the art understands them to indicate a lower numerical limit. Unless this leads to a contradiction apparent to a person skilled in the art, they will always interpret the terms "a" or "a" as meaning "at least one" or "at least one." This understanding is encompassed by the present invention, as is the interpretation that a numerical term such as "a" can alternatively be meant as "exactly one," whenever this is technically feasible to a person skilled in the art. Both are encompassed by the present invention and apply to all numerical terms used herein. Hatchmore Labs GmbH

[0046] When the terms “programmed”, “intended” or “configured” are used herein, it is also disclosed that these terms may be interchangeable in some embodiments.

[0047] When the term "programmed", "intended" or "configured" is used herein to perform a step or action, it is also disclosed that in some embodiments this step or action is optionally performed automatically, e.g. by the control device.

[0048] Whenever spatial terms such as "above," "below," "left," or "right" are used herein, a person skilled in the art understands this to mean the arrangement shown in the attached figures and / or in the operating state. "Below" is closer to the Earth's center or the lower edge of the figure than "above."

[0049] Advantageous further developments of the present invention are the subject of dependent claims and embodiments. Embodiments as disclosed herein further develop the invention as defined by the independent claims.

[0050] Whenever an embodiment is mentioned herein, it refers to an exemplary embodiment according to the invention, e.g. based on one of the independent claims, which is not to be understood as limiting.

[0051] If it is disclosed herein that the object of the invention has one or more features in a particular embodiment, it is also disclosed herein that the object of the invention expressly does not have precisely this or these features in other embodiments, which are also according to the invention, e.g., in the sense of a disclaimer. For each embodiment mentioned herein, the opposite embodiment, formulated, for example, as a negation, is therefore also disclosed.

[0052] Embodiments according to the invention may, for example, based on any one of the independent claims, have and / or consist of one or more of the features mentioned above and / or below. The features mentioned herein may be the subject of embodiments according to the invention in any combination, for example, based on any one of the independent claims or any part or combination or subcombination thereof, provided that a person skilled in the art does not recognize a specific combination as technically impossible.

[0053] Whenever a suitability, purpose, step or process step is mentioned herein, the present invention also includes a corresponding programming or configuration of a device or a section thereof suitable for achieving or carrying out the intended purpose.

[0054] According to the invention, a system for determining the time and / or dose of a drug to be administered to a patient is proposed.

[0055] The system comprises, or consists of, as functional components an electronic control device, a data storage device, a feedback device and an output device, in particular an information output device.

[0056] When the term "storage" is used herein, particularly of data and / or values, it may refer to a process or action by which the system described herein and / or a part of the system and / or one or more functional components and / or devices of the system store data, information, or computational results in a designated data storage medium in order to obtain or retain them for later retrieval, further processing, or long-term storage. Such an operation may include converting the data to be stored into a suitable format, assigning a specific storage location within the data storage medium, physically or logically writing the data to the storage medium, and, where appropriate, implementing mechanisms for data integrity, access control, and retrievability. Hatchmore Labs GmbH

[0057] Storage can be temporary or permanent, structured or unstructured, compressed or uncompressed, and also includes processes for updating, overwriting, or supplementing already stored data. The storage process can occur synchronously or asynchronously with data generation or processing and can utilize various storage technologies such as volatile or non-volatile memory, local or distributed storage systems, and physical or virtual storage environments.

[0058] The data storage device serves at least to store the administration times of one or more previously administered dosage forms of the drug and / or to store the dose (i.e., the amount) of these previously administered dosage forms of the drug.

[0059] In some embodiments, the data storage device contains the data mentioned for certain embodiments, e.g., the numerical values ​​disclosed herein, in particular in any combination. In some embodiments, they are taken into account in any combination.

[0060] The feedback device is used to record data, specifically patient data, regarding the patient's response to the administration of a particular dosage form of the drug. This data can include, for example, at least the occurrence of an effect, no effect, or side effects.

[0061] In connection with the invention described herein, any or all patient- and / or patient-related responses can be referred to as "feedback," whether generated by the patient and / or about the patient by another person, system, process, checklist, diagnosis (e.g., laboratory tests, assays), measuring and / or imaging device, implant, sensor, wearable device, etc. Furthermore, patient feedback may include information about the efficacy, safety, tolerability, and / or benefit of the drug therapy. For each of these concepts, patient feedback may include, among other things, information on the following:

[0062] 1. Biomarkers

[0063] A biomarker is a defined characteristic measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic interventions. Biomarkers can include molecular, histological, radiological, or physiological characteristics. A biomarker is not a measure of how a person feels, functions, or survives. Biomarkers can, for example,They are classified as response biomarkers, pharmacodynamic biomarkers, surrogate endpoints, validated surrogate endpoints, reasonably likely surrogate endpoints, candidate surrogate endpoints, safety biomarkers, predictive biomarkers, susceptibility / risk biomarkers, diagnostic biomarkers, monitoring biomarkers, prognostic biomarkers, and digital biomarkers.

[0064] 2. Clinical outcomes, such as ClinRO, ObsRO, PRO and PerfO.

[0065] The assessment of a clinical outcome can be based on a report from a physician, a patient, a non-clinical observer, or on a performance-based evaluation, such as:

[0066] 2.1. Clinician-reported Outcomes (ClinRO): A measurement based on a report prepared by a trained healthcare professional after observing a patient's health status. Most ClinRO measurements involve a clinical assessment or interpretation of observable signs, behaviors, or other manifestations related to an illness or condition. ClinRO measurements cannot directly assess symptoms known only to the patient. ClinRO measures include, but are not limited to, those developed by Hatchmore Labs GmbH.

[0067] Reports of specific clinical findings (e.g., presence of a skin lesion or swollen lymph nodes) or clinical events (stroke, myocardial infarction, death, hospitalization for a specific cause), which may be based on clinical observations along with biomarker data, such as electrocardiogram (ECG) and creatine phosphokinase (CPK) results, supporting a myocardial infarction. Assessment scales such as the Psoriasis Area and Severity Index (PASI) to measure the severity and extent of a patient's psoriasis and the Hamilton Depression Rating Scale (HAM-D) to assess depression.

[0068] 2.2. Observer-Reported Outcomes (ObsRO): A measure based on a report of observable signs, events, or behaviors related to a patient's health status by someone other than the patient or a healthcare professional. Generally, ObsROs are reported by a parent, caregiver, or someone who observes the patient in daily life and are especially useful for patients who are unable to report themselves (e.g., infants or individuals with cognitive impairments). An ObsRO measure does not include any medical assessment or interpretation. ObsRO measures may include, but are not limited to, the following:

[0069] Rating scales (e.g., Acute Otitis Media Severity of Symptoms Scale (AOM-SOS), a measure to assess signs and behaviors associated with acute otitis media in infants, and Face, Legs, Activity, Cry, Consolability Scale (FLACC), a measure to assess signs and behaviors associated with pain).

[0070] Counting of events (e.g., a log of seizure episodes generated by the observer).

[0071] 2.3. Patient-Reported Outcome (PRO) (or Patient-Reported Outcome Measure (PROM)):

[0072] A measure based on a report taken directly from the patient (i.e., the study participant) about their health condition, without the patient's response being altered or interpreted by a physician or other person. A PRO can be measured through self-report or interview, provided the interviewer records only the patient's response. Symptoms or other unobservable concepts known only to the patient can only be measured using PRO measures. PROs can also assess the patient's perspective on functioning or activities that can be observed by others. PRO measures can include, but are not limited to, the following:

[0073] Rating scales (e.g., numerical rating scale of pain intensity or Minnesota Living with Heart Failure Questionnaire for assessing heart failure). Counting of events (e.g., patient-completed log of vomiting episodes or urination episodes).

[0074] 2.4. Performance Outcome (PerFO): A type of clinical outcome assessment. It is a measurement based on standardized tasks actively performed by a patient according to a set of instructions. A PerFO assessment can be conducted by a suitably trained individual or performed independently by the patient. PerFO measures may include, but are not limited to, the following:

[0075] Measurements of walking speed (e.g., timed 25-foot walk test with a stopwatch or with sensors on the ankles) or distance (e.g., the 6-minute walk test, which is used, among other things, in pulmonary arterial hypertension)

[0076] Measurements of memory (e.g., word recall test)

[0077] In some embodiments, the feedback device has an input interface which is specifically configured to receive input from one of the above feedback examples, for example through specific queries to support the feedback provider, a specific input mask, and the like.

[0078] A “patient response to administration of a dosage form” is used herein in some embodiments to refer to any type of patient response following administration of a Hatchmore Labs GmbH

[0079] The term "patient reaction" refers to the administration of medication to a patient that is suitable or intended to provide information about a neutral, positive, or negative pharmacological effect of the drug. For example, a patient's discomfort after medication administration is a "patient reaction" and is suitable for providing information about drug tolerability. Similarly, a reduction in pain after administering a pain reliever is a "patient reaction" that, in this case, is suitable for providing information about the drug's effectiveness. Changes in laboratory values ​​in response to medication administration are also suitable for providing information about a neutral, positive, or negative pharmacological effect of the drug. Further examples include visually detectable changes in disease symptoms, such as findings or changes in an X-ray or computed tomography scan, etc.

[0080] The electronic control device, hereinafter also referred to as the control device, is programmed, among other things, to read data stored in the data memory and to evaluate patient data acquired by the feedback device. Furthermore, it is programmed to determine the timing and / or dose of the next or subsequent dosage form(s) of the drug, or when and in what dosage these should preferably be administered, preferably taking into account the data read from the data memory and / or the data acquired by the feedback device. This determination can involve making suggestions. Optionally, the data acquired by the acquisition device can also be included in this determination.

[0081] In some embodiments, the control device is designed as a computing device. The output device, particularly the information output device, can output information about the determined time(s) and / or dose(s) of the next or subsequent dosage form(s) of the drug. Such an output value or values ​​need not always be visible or displayed and can alternatively be included in the calculation without being displayed or output.

[0082] Alternatively or additionally, the next dosage form(s) can be dispensed using the dispensing device, for example, a medication delivery device. When the term "patient" is used here, it refers to a person who requires medication. This phrasing provides no information whatsoever regarding the person's gender or other characteristics.

[0083] When the term "user" of the system is used herein, it includes the patient who self-medicates, the nurse, the doctor, relatives of patients, and others who, for example, use the system as described herein at the patient's request when administering the patient's medication.

[0084] The term "medicinal product" is used herein to refer to an active pharmaceutical ingredient intended for the treatment or prophylaxis of diseases. It includes, for example, gene and cell therapies, but especially small molecule compounds and biologics with a desired biological activity. It is also disclosed to interchange these terms in some embodiments.

[0085] When the term "treatment" is used herein, it is also made clear that this may be or include a "treatment session".

[0086] Drug dosage forms can be administered via various routes, such as orally, parenterally (e.g., epidural, intramuscular, intradermal, or intravenous), or topically (e.g., nasally, buccally, or by inhalation). Preferred dosage forms are non-intravenous, particularly non-parenteral. Preferred dosage forms are oral dosage forms, such as tablets, capsules, granules, solutions, and suspensions for oral administration. Hatchmore Labs GmbH

[0087] When this text refers to "capturing," especially data and / or values, this may include investigating an existence or non-existence, determining, recording, measuring, collecting, evaluating, processing, comparing, estimating, assessing or gauging, discovering, calculating, obtaining, achieving and / or recognizing.

[0088] When the term "calculating" is used herein, it can refer to the process or action by which a system or device produces a specific output or result by applying mathematical, logical, or algorithmic operations to one or more input variables. This process can include performing arithmetic operations, applying formulas, conducting statistical analyses, solving equations, or executing complex algorithms. "Calculating" can be done in real time, iteratively, or based on predefined computational steps to produce quantitative or qualitative results. "Calculating" can also include reading data, for example, from a table of values ​​or a graph.

[0089] When the term "calculation" is used herein, it can refer to both the process of computation and the resulting outcome within a system or device. As a process, a calculation encompasses all mathematical or logical operations performed, including all intermediate steps and methods used. As a result, a calculation represents the final value or output generated by the computational process. A calculation can involve numerical values, vectors, matrices, logical states, or complex data structures and serves as the basis for further system operations, decision-making, or as output to the user or other system components.

[0090] In certain embodiments, administration times are also known as ingestion times. When the term "administration time" is used herein, it may refer in some embodiments to the time of ingestion or application by the patient, and in others to the time of administration (intravenously, intravenously, etc.) or application by the physician. The same applies to the term "administration," which may refer to administration by the physician, by means of an (automated) device such as a pump, or to ingestion or application by the patient.

[0091] Drug dosage forms can be administered via various routes, such as orally, parenterally (e.g., epidural, intramuscular, intradermal, or intravenous), or topically (e.g., nasally, buccally, or by inhalation). Preferred dosage forms are non-intravenous, particularly non-parenteral. Oral dosage forms, such as tablets, capsules, granules, solutions, and suspensions for oral administration, are also preferred.

[0092] Determining, in this context, can involve calculating, measuring, and / or reading. Determining can also involve making suggestions.

[0093] If this refers to determining the timing and / or dose of the next or subsequent dosage form(s) of the medicinal product, taking into account the data read and recorded, this may involve calculating, extracting, and / or reading data, or suggesting a time. The data read or recorded may play a role in this determination.

[0094] A “dosage form of a drug” is used herein to refer to the physical form in which the drug is administered. The term “drug” is used herein with the same meaning. Non-exhaustive examples of dosage forms include tablets, capsules, suppositories, solutions, suspensions, powders, aerosols, creams, emulsions, gels, granules, and numerous other dosage forms, such as those listed by the US FDA at the following link: https: / / www.fda.gov / industry / structured-product-labeling-resources / dosage-forms. Hatchmore Labs GmbH

[0095] When patient data is mentioned herein, in some embodiments this refers to data that captures or describes a patient response. A "patient response to the administration of a dosage form" is used herein in some embodiments to mean any type of reaction of the patient after administration of a drug that is suitable or intended to provide information about a positive or negative pharmacological effect of the drug. For example, a patient's discomfort after administration of a drug is a "patient response" and is suitable, for example, to provide information about drug tolerability. Similarly, for example, a reduction in pain after administration of an analgesic is a "patient response" which, in this case, is suitable to provide information about the drug's efficacy.Changes in laboratory values ​​in response to medication administration are also suitable, for example, for conveying information about a positive or negative pharmacological effect of the drug. Further examples include visually detectable changes in disease symptoms, such as changes or findings in an X-ray or computed tomography scan.

[0096] When this text refers to "reading data," particularly values, it can describe a systematic and purposeful process in which a system extracts information from one or more data sources, records it, and makes it available for further processing. Reading data forms one of the foundations for subsequent data processing and value calculation within the system and / or its components and / or devices.

[0097] When the term “evaluation of patient data”, in particular values, is used herein, the system and / or a part of the system and / or one or more functional components and / or devices of the system may perform a process and / or an action in which the collected medical, physiological and / or lifestyle information of a patient, as well as their responses to drug therapy, are subjected to systematic analysis and interpretation, in particular insofar as it was acquired by means of the feedback device.

[0098] This process optionally includes the aggregation, normalization, and correlation of various data points, including but not limited to demographic data, medical history, current symptoms, laboratory values, vital signs, medication history, therapy adherence, and desired and / or undesired drug effects.

[0099] The analysis optionally includes the application of pre-programmed algorithms, statistical methods, and / or machine learning to this data in order to identify relevant patterns, trends, or deviations. The goal of this analysis is preferably to generate a data-driven foundation for the subsequent calculation of an individualized drug dosage recommendation using a specific dosing algorithm. The analysis process can be performed in real time or at defined intervals and can include mechanisms to ensure data integrity, protect patient privacy, and guarantee the traceability of the analyzed information.

[0100] "Dose" is used here to refer to a measured or specific amount of a drug in a dosage form. If the drug is in salt form, the dose refers only to the pharmaceutically active component of the drug. For example, consider Adderal, which contains amphetamine salts. The dose stated in the package insert (10 mg, 20 mg, etc.) refers to the weight of amphetamine free base, and the counterions are not taken into account when determining the dose.

[0101] In certain embodiments, the dose is defined here as the amount of the administered drug, and can therefore be understood as the "dose level".

[0102] When this refers to "considering data," especially values, it can be an integrative process within the system, in which specific data sets or data information are actively incorporated into the processing, analysis, and calculation algorithms. (Hatchmore Labs GmbH)

[0103] In particular, dosing algorithms are included to generate precise and context-relevant results below the individual patient level and / or (sub)population level.

[0104] When this document refers to the "output of information," particularly values, it may mean a process and / or action in which the system listed herein and / or a part of the system and / or one or more functional components and / or devices, after performing one or more calculations, analyses, or processing steps, provide the resulting data, results, or derived insights in a form perceptible and interpretable to the user. This process optionally includes converting the internally processed data into a suitable output format, selecting the relevant information, adapting the presentation to the intended output interface, and actually transmitting the information to the user.The "output of information" can occur through various modalities, including but not limited to visual representations on screens or displays, acoustic signals or speech output, haptic feedback, printed documents, or transmission to external devices or systems for further processing or display. The output process can occur in real time or with a time delay relative to computation, can be interactive or automated, and can encompass various formats, levels of detail, or levels of abstraction of the information to meet the specific requirements of the user or application.When the term “dispensing a dosage form” is used herein, it may refer to a process and / or action whereby the system and / or part of the system and / or one or more functional components and / or devices of the system, after performing one or more calculations, analyses or processing steps, provides information regarding the next or subsequent dose and / or dosage form of a medicinal product in a form perceptible and interpretable to the user or a downstream system.

[0105] This process may include, among other things, determining the optimal or recommended dosage parameters based on predefined algorithms, patient-specific data, pharmacokinetic models and / or medical guidelines, as well as subsequently formulating this information into a concrete instruction or recommendation.

[0106] Furthermore, "dispensing a dosage form" can include specifying the drug form (e.g., tablet, capsule, solution), the amount of active ingredient, the time of administration, the frequency of administration, and / or special instructions for use. The dispensing can be in various formats, including but not limited to textual instructions, graphical representations, coded signals for automated dosing systems, or structured datasets for integration into electronic health records or medication management systems. The dispensing process can occur immediately after calculation or at a predefined time and may include mechanisms to ensure data integrity, user authentication, and traceability of the dispensed dosage information.

[0107] Furthermore, "dispensing a dosage form" can refer to the physical administration of the medication, for example, using a medication dispenser. This means that the information can be conveyed by dispensing the medication itself. In this case, the dose and the timing of the medication administration embody the information.

[0108] When the timing of the next or further dosage form(s) is mentioned herein, in some embodiments this is to be understood as a recommendation (directly or indirectly) to the patient as to what time, day, day, and date the system suggests taking the next or further dosage form(s).

[0109] When the next or further dosage form(s) are mentioned herein, in some embodiments this is to be understood as a recommendation (directly or indirectly) to the patient as to the quantity of drug the system suggests to take or Hatchmore Labs GmbH

[0110] To understand how to take or use the next or further dosage forms.

[0111] In some embodiments, the data storage includes pharmacological, pharmacodynamic, pharmacometric, pharmacokinetic and / or pharmacogenetic data relating to the drug to be administered and / or one or more active metabolites thereof.

[0112] The term “pharmacogenetic data” is used herein to refer to information that reflects the effect of the drug on the patient based on their individual genotype, in particular the effect of a particular genotype on the variability of drug action, the variability of drug toxicity and / or the variability of the pharmacokinetic parameters of a drug.

[0113] Pharmacogenetics, sometimes also called pharmacogenomics, is a subfield of pharmacology that studies how a person's genes influence their action and response to drugs. This research aims to understand the effects and interactions between drugs and individuals based on their genetic makeup in order to predict drug effects in individuals, and / or to personalize drug dosages, and / or to optimize the dose-to-effectiveness ratio, and / or to minimize unwanted side effects and toxicity. Pharmacogenetic information is collected, for example, to determine in advance which drug or dose of a drug is most suitable for a person.These tests often analyze genes of the CYP group (CYP1, CYP2, CYP3, CYP4) because the enzymes they encode are involved in the metabolism of most common drugs.

[0114] The term "pharmacological data" is used in some versions herein to refer to information about the effects and mechanisms of action of a drug on a biological system, such as a patient. Pharmacology is the science of the interaction between substances and living organisms. It investigates the biological effects and mechanisms of action of drugs with the aim of controlling biological processes and influencing pathological processes.

[0115] The term “pharmacokinetic data” is used herein to refer to information about how, or how quickly, a drug is absorbed, distributed, metabolized, and / or eliminated by a patient’s body. Non-exhaustive examples of pharmacokinetic data for a drug include its bioavailability in the context of a dosage form, its volume of distribution, its onset kinetics after administration, its half-life in various tissues or in blood plasma, and its clearance.

[0116] Pharmacokinetics is a subfield of pharmacology that describes the behavior of a drug in the human body. It encompasses all the processes a drug undergoes in the organism. These processes are often summarized by the acronym LADME:

[0117] Liberation (release)

[0118] Absorption (uptake into the bloodstream)

[0119] Distribution (distribution within the organism)

[0120] Metabolism (metabolic processes)

[0121] Excretion

[0122] Pharmacokinetic data are important for physicians when prescribing medications to determine the correct dosage and ensure appropriate efficacy. In clinical practice, pharmacokinetics is used, for example, in therapeutic drug monitoring, where drug concentrations in body fluids are measured to optimize therapy. The mathematical foundations of pharmacokinetics are described in detail, for example, in Gugeler and Klotz, "Introduction to Pharmacokinetics" (2000), 2nd edition, GOVI-Verlag. The complete contents of this book are incorporated herein by reference as part of this application. Hatchmore Labs GmbH

[0123] The term "pharmacodynamic data" is used here to refer to information about the effects of a drug on a biological system. This term encompasses both therapeutically desired effects and undesired effects.

[0124] Pharmacodynamics refers to the effects a drug has on a patient's body. Non-exhaustive examples of pharmacodynamic data include dose-response (DR) relationships, dose-exposure (DE) relationships, dose-exposure-response (DER) relationships, the value for the maximum therapeutic concentration of the drug, and the value for the minimum therapeutically effective concentration of the drug.

[0125] Pharmacodynamics is the study of the effects of drugs in the body and is a subfield of pharmacology. It describes what a drug does in the body, in contrast to pharmacokinetics, which deals with how the body reacts to the drug. Aspects of pharmacodynamics include, for example, the action profile of a drug, i.e., information about the type and location of a drug's effect, including the organs, structures, or biological functions affected; or, for example, the mechanism of action of a drug, i.e., information describing how a drug acts in the body at the molecular level; or, for example, dose-response (DR) relationships; or, for example, dose-exposure-response (DER) relationships, such as information describing the relationship between drug concentration and clinical effect; or, for example,

[0126] Interaction studies, i.e., information on how a drug interacts with other molecules.

[0127] The term "pharmacometric data" is used here to refer to quantitative information that can be used for modeling. This includes, for example, the terms "pharmacokinetics" and "pharmacodynamics," as well as patient-specific physiological data such as age, weight, biological sex, and genotype, and demographic data such as the dependence of disease severity on physiological parameters, e.g., an age-dependent case fatality rate.

[0128] Pharmacometry is an interdisciplinary science at the interface between biology and mathematics, which uses mathematical models to predict and describe the interactions between drugs and the human body.

[0129] For example, pharmacometry uses computer-aided mathematical models, statistical analyses of data from clinical trials, and information on interindividual variability from population studies to, for example, model the time course of drug concentrations and / or predict desired and undesired effects of drugs and / or determine the optimal dosage and frequency of administration of medications and / or predict the course of disease and the effectiveness of therapies.

[0130] When the term "active metabolite" is used herein, it refers, in certain formulations, to a metabolic product of the drug itself that exhibits biological activity. It may be formed, for example, in the patient's body through oxidation, reduction, hydrolysis, or derivatization of the drug or one of its metabolites. Active metabolites often retain the same type of biological activity as the drug, for example, by binding to the same receptor or target molecule. An active metabolite of a drug may have less, more, or the same potency as the drug itself. An example of an active metabolite with higher biological activity is ACT-333679, an active metabolite of 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide.

[0131] When the term "active metabolite" is used herein, it refers in certain embodiments to a specific metabolite or at least a metabolite.

[0132] In some embodiments, these pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data (relating to the drug and / or one or more active metabolites) are or include pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic Hatchmore Labs GmbH

[0133] and / or pharmacokinetic models relating to the drug and / or one or more of its active metabolites.

[0134] In one embodiment, the invention is based on PK / PD modeling to provide a drug dosing system which, based on efficacy, safety, and / or tolerability responses, can determine the individual treatment benefit for each patient in order to optimize drug therapy individually. The PK / PD modeling comprises a comprehensive range of flexible models to simultaneously describe how PK and PD change over time, with the PD changes over time being determined by the PK changes over time (possibly with a delay to be taken into account).

[0135] However, the system described herein can also use parts or combinations of other types of modeling approaches (which require minimal to no PK information) to achieve this goal, such as, but not limited to:

[0136] “Mechanistic (PKPD)” models;

[0137] “Direct Dose-Response (DR)” and / or “Exposure-Response (ER)” models;

[0138] “Physiologically-Based Pharmacokinetic (PBPK)” models;

[0139] “Population Pharmacokinetics (PopPK)” models;

[0140] “Virtual Bioequivalence (VBE)” models (sometimes also part of PBPK or PopPK models);

[0141] “Pharmacometrics models”, e.g. “Pharmacometrics Simulations” and “Model-Based Drug Development (MBDD)” models;

[0142] “Therapeutic Drug Monitoring (TDM)”;

[0143] “Model-Informed Drug Development (MIDD)” models;

[0144] “Model-Informed Precision Dosing (MIPD)” models;

[0145] "Pharmacogenetic Models";

[0146] “Allometric Scaling Models”;

[0147] “Bayesian Inference” models and approaches;

[0148] “Integrated PKPD Toxicity” models;

[0149] “Quantitative Systems Pharmacology (QSP)” models;

[0150] “Disease progression” models;

[0151] “Machine Learning” and “AI-Based” models;

[0152] “Time-to-Event (TTE)” models;

[0153] “Kinetic-Pharmacodynamic (KPD)” models;

[0154] “Simplified Kinetics” models;

[0155] “Non-Compartmental Analysis (NCA)” models.

[0156] In some embodiments, the data storage includes numerical values. These numerical values ​​describe, in particular, what proportion of the drug from a given dosage form is absorbed by the body. Alternatively or additionally, they describe how the drug is distributed in the body, e.g., within which distribution spaces, in what proportions it is distributed within different distribution spaces, etc.

[0157] When the patient's body is mentioned herein, this can be understood to mean the entire body excluding the contents of the gastrointestinal tract.

[0158] Alternatively or additionally, they describe how long it takes for the concentration of the drug in the blood plasma to reach a maximum after administration of a dosage form of the drug and / or how long it takes for the concentration of an active metabolite of the drug in the blood plasma to reach a maximum after administration of a dosage form of the drug.

[0159] Blood plasma, as used here, refers to the non-cellular component of whole blood. It is a clear, yellowish fluid that makes up about half of whole blood. It consists of approximately 90% water and contains, for example, proteins, salts, sugars, minerals, and hormones. Hatchmore Labs GmbH

[0160] The concentration of a substance (e.g., a drug) is defined here as the quotient of the amount of the substance and the reference volume containing that amount of the substance. Plasma concentration or blood plasma concentration is defined here as the concentration of a substance, e.g., the drug or an active metabolite of the drug, in the blood plasma.

[0161] Alternatively or additionally, the numerical values ​​describe how quickly the plasma concentration of the drug decreases per unit of time and / or how quickly the plasma concentration of the drug's active metabolites decreases per unit of time.

[0162] In this context, a unit of time refers to a quantity of time, e.g., a quantity of a unit of measurement that allows for quantitative statements about time as a physical quantity. Examples of units of time are seconds, minutes, hours, or days.

[0163] Alternatively or additionally, they describe the amount of the drug that is excreted from the body per unit of time and / or the amount of the drug's active metabolites that are excreted from the body per unit of time.

[0164] In this context, "excretion from the body" refers to the release of substances from the body's interior into the external environment. Substances can be excreted, for example, via feces, urine, or sweat.

[0165] Alternatively or additionally, the numerical values ​​describe which concentration of the drug is assigned to a desired drug effect; and / or which concentration of the active metabolite(s) of the drug is assigned to a desired drug effect.

[0166] When active metabolites are mentioned herein, this can refer to the singular (exactly one active metabolite) as well as, alternatively, the plural (several active metabolites). Both alternatives are encompassed by the present invention, as is the use of only the singular or only the plural.

[0167] The term "desired drug effect" here refers to the therapeutically desired effect of a drug, i.e., the effects that contribute positively to the treatment of a disease, such as the disease for which the drug is approved or, for example, a disease for which the drug is used by physicians without being approved for that purpose. An example of a desired drug effect is the pain-relieving effect of fentanyl, which is desirable in the treatment of severe, often chronic pain. When a desired drug effect is mentioned here, it can be defined qualitatively, for example, using descriptive terms such as "insufficient," "adequate," "good," etc. A desired drug effect can also be specified quantitatively, for example, using grades, similar to school grades.A range of well-being, with regard to the desired effect of the medication (relief from pain, itching, etc.), can be defined, for example, as a specific input field on a touchscreen display associated with the feedback device, a form, etc., which preferably only allows entries with the expected format (similar to "dd.mm.yy" for entering a date and nothing else), within which the patient expects to feel after taking the medication. A range, a threshold, etc., can be specified for the desired effect of the medication.

[0168] Alternatively or additionally, the numerical values ​​describe which concentration of the drug is attributed to an adverse drug reaction and / or which concentration of the active metabolite(s) of the drug is attributed to an adverse drug reaction.

[0169] The term "adverse drug reaction" here refers to any unwanted, unpleasant, or dangerous effect of a drug. This includes, for example, side effects, which are mostly undesirable effects that occur when the Hatchmore Labs GmbH product is used as prescribed.

[0170] This includes all adverse effects that can occur with a drug, such as harmful, unintended effects or effects simply perceived as undesirable by the patient. The term also encompasses the toxicity of a drug.

[0171] Examples of adverse drug reactions include:

[0172] Adverse Effect (AE), Adverse Drug Effect, Adverse Reaction, Adverse Drug Reaction (ADR) (side effect or undesired drug effect)

[0173] Toxic effect

[0174] Unexpected adverse reaction

[0175] Serious adverse effects

[0176] Adverse Event / Adverse Experience (adverse event / adverse experience) Drug Hypersensitivity Reaction (DHR) (drug hypersensitivity reaction) Non-Immune Drug Hypersensitivity Reaction (non-immune drug hypersensitivity reaction)

[0177] Immediate Drug Hypersensitivity Reaction (I GV)

[0178] Non-immediate Drug Hypersensitivity Reaction (NIHR)

[0179] Drug allergy

[0180] Type A (“enhanced”) reactions

[0181] Type B ("bizarre") reactions

[0182] Type C ("continued") reactions

[0183] Type D ("delayed") reactions

[0184] Type E ("End-of-Use") reactions

[0185] The term "assignment of a concentration to an effect" refers, for example, to a dose-response (DR) relationship for a drug, such as a DR curve or dose-exposure-response (DER) curve stored in a data repository. In this context, a drug concentration in a compartment, such as blood plasma, is assigned to an expected value for the onset of a desired drug effect in a patient at that concentration. An example of such a DR curve is the sigmoidal Emax model with four parameters.

[0186] This model can be defined as follows:

[0187] E = EO + (Emax * Dose / ) / (Dose / ) + ED50 / )

[0188] where E represents the effect, EO is the effect associated with dose = 0 (e.g., a placebo response rate), Emax is the maximum drug effect, ED50 is the dose required to achieve 50% of Emax, and y is the Hill coefficient that defines the slope of the dose-response relationship (under an alternative parameterization, this model is also known as the logistic 4-parameter model).

[0189] This model is described in detail at https: / / www.icp.org.nz / pharmacodynamics / linear-vs-log-graphs. This detailed description is incorporated herein by reference.

[0190] Two common representations of the ER curve are particularly suitable for explaining exposure-response relationships: the logarithmic and linear representations of the ER curve. For example, the linear representation shown below shows that above ED50, a doubling of the dose does not lead to a doubling of the effect.

[0191] For most drugs, therapeutic doses are likely to be above the ED50 value for efficacy endpoints. This means that while doubling the dose may lead to a higher response rate, the additional benefit may not be as great as hoped. Conversely, for most safety and tolerability endpoints, therapeutic doses are likely to be below the ED50 value. This is because such doses for these endpoints are typically found in Hatchmore Labs GmbH.

[0192] The lower part of the DR curve is located. For example, one might expect 10-40% of patients to experience nausea at therapeutic doses, rather than 60-90%.

[0193] In the lower part of the dose-response (DR) relationship, doubling the dose generally leads to a larger "jump" in effect. For example, from an effect of 20 points on a scale at 2.5 mg to an effect of 33 points at 5 mg (a relative increase of 65%). Therefore, when titrating drugs, it is generally safety and / or tolerability considerations, rather than efficacy, that determine the extent and timing of dose titrations. To ensure that the correct dose can be found most efficiently for each individual, it is particularly necessary to understand the interindividual variability in the location (ED50i) and steepness (Hill-i) of the safety curves.

[0194] Since most medications are dosed significantly above the ED50 for efficacy endpoints, it is also useful to compare the increase in response between two higher doses, for example, 40 mg (4*ED50) compared to 20 mg (2*ED50). In this case, the response ratios are 1.14, 1.20, and 1.18 for Hill coefficients of 0.5, 1, and 1.18, respectively.

[0195] 2. For even higher doses, e.g. 100 mg (10*ED50) compared to 50 mg (5*ED50), the response ratios are 1.10, 1.09 and 1.03 for Hill coefficients of 0.5, 1 and 2 respectively.

[0196] The most important finding is that the higher the dose is above the ED50, the lower the additional benefit. In contrast, the dose values ​​relevant for safety and / or tolerability endpoints are generally below the ED50, so doubling the dose leads to a proportionally greater increase in (adverse) reactions.

[0197] In the case where a shallow (Hill=0.5) DR relationship exists, a doubling of the dose may have only a very small change in efficacy, safety and / or tolerability, whereas in the case of a steep (Hill=2) DR relationship, a doubling of the dose may have a significant effect if the dose is in the lower or middle part of the DR range and a minimal effect at higher doses.

[0198] In some embodiments, the numerical value describing the proportion of the drug from a given dosage form that is absorbed by the body may be, or include, the bioavailability of the drug in that dosage form. Here, bioavailability is a measure of the proportion (in %) of an administered drug that reaches the blood, and in particular the blood plasma, upon administration. It is a measure specific to a particular dosage form of a drug, not to the drug itself. Bioavailability is determined by the pharmaceutical formulation, the solubility and absorbability of the drug in the body, and the external conditions under which experimental measurements are performed to determine bioavailability.Therefore, bioavailability is a complex quantity that cannot be considered an absolute or fixed parameter for a drug dosage form. It only applies to the conditions under which it was measured. According to the guidelines of the U.S. Food and Drug Administration (FDA), it is defined as follows: "Bioavailability means the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action."

[0199] Accordingly, bioavailability includes, for example, the rate and / or extent with which the active ingredient (the drug) is absorbed from its pharmaceutical form and is present at the site of action, or is released from a pharmaceutical form into the systemic circulation. For an intravenously administered dose, bioavailability is, by definition, 100 percent. To determine absolute bioavailability in an intraindividual comparison, an IV administration is necessary, to which the pharmacokinetic data refer, for example, after oral, sublingual, transdermal, subcutaneous, or intramuscular administration (these are not exhaustive examples). Bioavailability, as measured in population studies, serves as a useful starting point for its initial assessment at the beginning of treatment with the system according to the invention. Hatchmore Labs GmbH

[0200] The stored value can be determined, but it can vary from individual to individual, and its value is therefore individually adjusted in embodiments according to the invention.

[0201] Alternatively or additionally, the numerical value that describes how the drug is distributed in the body can be or indicate the volume of distribution of the drug.

[0202] The volume of distribution (Vd) is understood here as the hypothetical volume of a human or animal body into which a specific active ingredient or drug would have to distribute itself to explain the observed concentration in the blood plasma. The volume of distribution is a calculated value. It is normalized to body mass and expressed in liters per kilogram. For a detailed explanation of how the volume of distribution can be determined for various drugs with different pharmacokinetic properties, please refer to the book "Introduction to Pharmacokinetics" by Gugeler and Klotz (2000), 2nd edition, where the mathematical relationships used to calculate the volume of distribution are explained in detail on pages 34 to 38.The distribution volume, as it can be determined in population studies as a useful starting point for its value stored in the data memory at the beginning of a treatment with the system according to the invention, can vary from individual to individual, and its value is therefore individually adjusted in embodiments according to the invention.

[0203] In some embodiments, the numerical value describing how long it takes for the drug concentration in the blood plasma to reach a maximum after administration of a dosage form of the drug may alternatively or additionally be the "time-to-peak concentration" and / or the numerical value describing how long it takes for the concentration of the active metabolite of the drug to reach a maximum after administration of a dosage form of the drug, the "time-to-peak concentration" of the active metabolite.

[0204] In some embodiments, "time-to-peak concentration" refers to the time that elapses between the administration of a dosage form of a drug and the reaching of a maximum drug concentration in a compartment, such as an effect compartment. It is expressed in a unit of time, such as hours, and in some embodiments allows, for example, the determination of the absorption rate of a drug after administration of a dosage form.

[0205] The “time-to-peak concentration”, as described, for example, in the scientific literature or as a useful starting point for determining its value stored in the data storage at the beginning of treatment with the system according to the invention, can vary from individual to individual, and its value is therefore individually adjusted in embodiments according to the invention.

[0206] In this context, a maximum represents a local upper extreme value. For example, it is a temporal upper extreme value of a drug concentration, e.g., in a compartment or in the blood, that occurs after the administration of a drug. A "next maximum" is used here to denote the maximum that lies closest in the future to a given point in time.

[0207] Alternatively or additionally, the numerical value describing how quickly the plasma concentration of the drug decreases per unit of time can be the plasma half-life of the drug and / or the numerical value describing how quickly the plasma concentration of an active metabolite of the drug decreases per unit of time can be the plasma half-life of the active metabolite of the drug.

[0208] Blood plasma half-life is used here to indicate the time it takes for the concentration of a drug in blood plasma to decrease from a baseline level to half its initial value. For a detailed explanation of how the blood plasma half-life is determined for various drugs with different pharmacokinetic behavior, see Hatchmore Labs GmbH.

[0209] For further information, please refer to the book by Gugeler and Klotz, "Introduction to Pharmacokinetics" (2000), 2nd edition, in which the mathematical relationships according to which the blood plasma half-life can be determined are explained in detail on pages 41 and 42. The blood plasma half-life, as it can be determined in population studies as a useful starting point for its value stored in the data memory at the beginning of treatment with the system according to the invention, can vary from individual to individual, and its value is therefore individually adjusted in embodiments of the invention. The terms used herein for half-lives in whole blood or half-lives in another compartment, such as the effect compartment, are used analogously.

[0210] In some embodiments, the numerical value describing the amount of the drug eliminated from the body per unit of time can be the drug clearance and / or the numerical value describing the amount of the drug's active metabolite eliminated from the body per unit of time can be the drug's active metabolite clearance.

[0211] Clearance is used in some formulations to indicate the volume of blood, e.g., in milliliters, that is cleared of the drug in question per unit of time, for example, per minute or per hour. In this context, systemic clearance is generally used, which is the sum of all drug elimination processes, particularly renal and hepatic clearance. For a detailed explanation of how clearance can be determined for various drugs with different pharmacokinetic behavior, see the book "Introduction to Pharmacokinetics" by Gugeler and Klotz (2000), 2nd edition, where the mathematical relationships used to determine clearance are explained in detail on pages 43 to 65.However, the clearance, as it can be determined in population studies as a useful starting point for its value stored in the data memory at the beginning of a treatment with the system according to the invention, can vary from individual to individual, and its value is therefore individually adjusted in embodiments according to the invention.

[0212] In some embodiments, the numerical value describing the concentration of a drug associated with a desired drug effect can be a therapeutically effective minimum concentration in an effect compartment, and / or the numerical value describing the concentration of the drug's active metabolite associated with a desired drug effect can be a therapeutically effective minimum concentration of the active metabolite in an effect compartment. Such a numerical value is optionally stored and / or taken into account.

[0213] The term "therapeutically effective minimum concentration" is used herein to indicate the lowest concentration of a drug in an effect compartment at which the drug achieves a desired therapeutic effect. According to the invention, this is the value stored in the system as the "therapeutically effective minimum concentration." It must be reached for the treatment to be effective. The therapeutically effective minimum concentration varies depending on the drug. The therapeutically effective minimum concentration, as described, for example, in the scientific literature or as determined based on data from drug approval studies, is a useful starting point for its value stored in the data memory at the beginning of treatment with the system according to the invention. However, this value can vary from individual to individual and is therefore individually adjusted in embodiments of the invention.

[0214] The therapeutically effective minimum concentration (TEC) represents the lowest concentration of a drug in blood plasma that produces the desired therapeutic effect in a patient. It is an important concept in pharmacology and therapeutics, as it helps in determining appropriate dosing regimens to maintain drug levels above this threshold, thereby achieving optimal efficacy while minimizing potential side effects.

[0215] In some embodiments, the numerical value that describes which concentration of the drug is attributed to an adverse drug reaction can be a therapeutic Hatchmore Labs GmbH

[0216] acceptable maximum concentration in an effect compartment and / or the numerical value that describes which concentration of the drug's active metabolite is associated with an adverse drug reaction, a therapeutically acceptable maximum concentration of the active metabolite in an effect compartment.

[0217] The term "therapeutically acceptable maximum concentration" is used herein to indicate the highest concentration of a drug in an effect compartment at which, in some embodiments, undesirable, relevant, or intolerable drug effects do not yet occur, or above which undesirable drug effects, such as drug toxicity, are observed. This value is important to ensure that the treatment is safe. According to the invention, the "therapeutically acceptable maximum concentration" is the value stored in the system as the "therapeutically acceptable maximum concentration." The therapeutically acceptable maximum concentration varies depending on the drug. The therapeutically acceptable maximum concentration, as it is defined, for example, by...The value described in the scientific literature or determined based on data from drug approval studies is a useful starting point for its value stored in the data memory at the beginning of treatment with the system according to the invention. However, this value can vary from individual to individual and is therefore individually adjusted in embodiments according to the invention.

[0218] In an alternative interpretation, the therapeutically acceptable maximum concentration (TOC) represents the highest concentration of a drug in blood plasma that can be administered without causing unacceptable toxicity or adverse effects in patients. It is an important concept in pharmacology and drug development because it helps to establish the upper limit of a drug's therapeutic window and to balance efficacy with safety considerations. This term is sometimes also referred to as the maximum tolerable dose, maximum acceptable concentration, and / or maximum therapeutic concentration.

[0219] In some embodiments of the system, the data storage also includes or contains values ​​that encompass the statistical distribution for one, several, or all of the mentioned and / or stored values.

[0220] Such values ​​may also include statistical variances for one, several, or all of the numerical values ​​mentioned.

[0221] In some embodiments, the data storage includes, instead of or in addition to the distribution or variance, at least one further measure of distribution or dispersion, such as the standard deviation, the standard deviation, etc. The terms "distribution" or "variance" are therefore not to be understood restrictively here. In some embodiments, they can be supplemented or replaced by other measures, such as those mentioned above.

[0222] In some embodiments, the values ​​relating to the statistical distribution of the numerical values ​​refer to pharmacokinetic and / or pharmacodynamic individual patient values ​​(N=1) and preferably population studies. In particular, the values ​​relating to the statistical distribution of the numerical values ​​represent the variance and / or standard deviation of the relevant values ​​in pharmacokinetic and / or pharmacodynamic population studies.

[0223] When this text refers to a "statistical distribution," it can describe the frequency or probability with which certain values ​​or events occur in a data set or population. It can represent the relationship between a random variable and its probabilities and indicates how the values ​​of a characteristic are distributed over a specific range.

[0224] The statistical distribution mentioned herein can include both discrete and continuous random variables. In discrete distributions, the variables take on precise, isolated forms. Hatchmore Labs GmbH

[0225] numerical values, while continuous distributions can take on infinitely many values ​​within a given range.

[0226] Mathematically, statistical distribution can be described by various functions, such as the cumulative distribution function, the probability density function, or the probability function. These functions make it possible to calculate the probability of certain values ​​or ranges of values ​​occurring and to make predictions about future events.

[0227] When the term "standard deviation" is used here, it can serve as a measure of the dispersion of values ​​around the mean of a distribution. It can be defined as the positive square root of the variance and thus provides a quantification of the average deviation of the data points from the arithmetic mean in the original unit of measurement of the data.

[0228] In some embodiments, a population study is understood to mean a clinical study involving at least 10, preferably at least 30, individuals. Clinical studies are conducted as part of drug development and approval, and within the scope of such studies, pharmacokinetic and pharmacodynamic parameters are regularly determined at the population level. These parameters typically form the basis for the pharmacokinetic and pharmacodynamic parameters stored in the data memory at the beginning of treatment with the system according to the invention. However, the term also encompasses post-approval studies or studies published in the scientific literature involving multiple patients.

[0229] In some embodiments, the system further includes a writing device which is programmed to write or overwrite one, several, or all of the aforementioned numerical values ​​in the data memory during a process. It can be instructed to write or overwrite by the control device.

[0230] In some embodiments, the control or writing device is programmed to individualize one, several, or all of the aforementioned numerical values, particularly those stored or to be stored in the data memory, during the course of a patient's treatment, tailored to or for the individual patient. In particular, the system can recognize individual physiological characteristics of the patient if, for example, their response to the administration of a dosage form of the drug differs from what would be expected for an average patient with regard to drug effect and / or drug side effect(s) and / or the observed pharmacokinetics.While, as a rule, at the beginning of treatment the data storage contains values ​​for pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic parameters that were taken from the scientific literature or obtained on the basis of the data collected in the context of the approval studies, the system according to the invention makes it possible to recognize deviations of the patient from such an assumed “norm” and to individualize one or more of these parameters.

[0231] In some embodiments, the system is programmed such that the value for a therapeutically effective minimum concentration of the drug in an effect compartment and / or the value for a therapeutically effective minimum concentration of an active metabolite of the drug in an effect compartment, stored in the data memory, can be changed and optionally is changed during the course of treatment. Such a change may include overwriting, replacing, or supplementing with a more recent value.

[0232] A “body compartment” is used here to describe a pharmacokinetic concept. It is an imaginary unit that groups together tissues with similar drug distribution rates. The specific tissues comprising a compartment need not be known, and the number of compartments selected for a particular drug is based on the behavior of the drug concentrations in the blood observed over time. Hatchmore Labs GmbH

[0233] The number of compartments for a particular drug depends on the behavior of its concentrations in the blood. For example, one or two additional compartments may exist, separate from the central compartment, if the curve of the drug's plasma concentration over time shows that a significant amount of the drug is distributed to some tissues at a different, for example, slower, rate. In pharmacokinetics, the transport of substances into, out of, and between the different compartments is generally described by rate constants (first-order reactions).

[0234] In some embodiments, an effect compartment may be understood as that compartment in which the drug is supposed to show effect (as the reason for its prescription), i.e., in which it is supposed to bind to receptors, intervene in processes, etc.

[0235] The term "effect compartment" is used here to refer to the pharmacokinetic compartment that comprises the site of action of the drug or its active metabolite, i.e., the organ or group of cells whose function is or are intended to be affected by the drug, for example, by the drug binding to its pharmacological target there. In a one-compartment model, the effect compartment is the one compartment of the model. In a two- or multi-compartment model, the effect compartment may be the central or peripheral compartment, or a specific one of the peripheral compartments, and often it is the peripheral compartment or a specific one of the peripheral compartments in such a case.

[0236] In some embodiments, the system is further programmed to modify the stored value for a therapeutically acceptable maximum concentration of the drug in an effect compartment and / or the value for a therapeutically acceptable maximum concentration of the drug's active metabolite in an effect compartment during the course of treatment, for example, to overwrite, replace, or supplement it with a more current value. In some embodiments, the system also includes a detection device for optionally recording a drug administration pattern to the patient. This administration pattern optionally includes at least the time of administration and the dose of the most recently administered dosage form of the drug.

[0237] In some embodiments, an administration pattern is understood to mean a history of drug administration to the specific patient, for example since the start of treatment with the specific drug, or from information from previous treatments with this or another drug.

[0238] In some embodiments, the electronic control device is further programmed to evaluate the administration pattern detected by the sensing device. Determining the timing and / or dose of the next or subsequent dosage form(s) of the drug to be administered to the patient is then carried out taking into account the detected administration pattern or its evaluation.

[0239] In some embodiments, the administration pattern is or includes the time(s) of administration and the dose(s) of all administered dosage forms of the drug.

[0240] In certain embodiments, evaluating or taking into account the administration pattern detected by the detection device includes evaluating or taking into account the time(s) of administration and the doses.

[0241] In some embodiments of the system, the recording device is programmed to additionally record data on the patient's food intake.

[0242] This data can be collected, among other ways, through manual entry, e.g., using digital diaries or smartphone apps in which the patient records meals and / or portion sizes. Hatchmore Labs GmbH

[0243] entries, as well as scanning codes, e.g. barcodes or QR codes on food packaging using a mobile application.

[0244] Data collection can also be automated, for example, by using sensors in the oral cavity to detect chewing movements and swallowing, cameras or spectrometers for optical recognition and analysis of food, and / or implantable sensors to measure gastric activity or nutrient absorption in the digestive tract. Components used for this purpose, such as the sensors mentioned herein, can be part of the system.

[0245] Data can be collected via indirect measurements, such as continuous glucose monitoring to estimate carbohydrate intake, and / or analysis of biomarkers in body fluids to determine nutrient intake.

[0246] Data collection can also be environment-based, for example, through smart kitchen appliances such as refrigerators or stoves that log meal preparation and consumption, and / or weight sensors in plates or cutlery to measure the amount of food consumed. These methods can be used individually or in combination to obtain a comprehensive and accurate picture of the patient's food intake.

[0247] In some embodiments, "food intake data" refers to data concerning the quantity, timing, type, and / or route of food ingested by a patient. Food intake can affect drug absorption by, for example, influencing gastric emptying kinetics, gastric pH, or bile flow, so food intake data may be relevant to the pharmacokinetic considerations addressed here in some embodiments.

[0248] Such data include, in particular, data that could affect the kinetics or dynamics of the drug.

[0249] This data can be entered, for example, via an interface and can include, for example, the amount of food, nutritional value, carbohydrate content, protein content, fat content, water content, vitamin content, salt content and / or the time or period of food intake.

[0250] In particular, such data may be limited to a period before or during the administration of dosage forms, before or during therapy using the drug and / or another period.

[0251] In some embodiments, the detection device is programmed to detect individual physiological parameters of the patient, in particular additionally.

[0252] Individuals differ in their individual physiological parameters, such as weight, age, height, body mass index (BMI), and so on. Individual physiological parameters can influence the pharmacokinetics and / or pharmacodynamics of a drug, so that data on individual kinetic parameters may be relevant for the pharmacokinetic and pharmacodynamic considerations in connection with the system according to the invention in some embodiments. Alternatively or additionally, the detection device also acquires data indicating circumstances that alter the kinetics or dynamics, in particular the presence of liver and / or kidney insufficiency, enzyme deficiencies, and / or the like, as well as data from registration or other studies. This data can, for example, be entered into the detection device by the patient themselves or by a treating physician.

[0253] In some embodiments, the individual physiological parameters include known impairments of the patient, particularly in the area of ​​metabolism or excretion of drugs or active metabolites, such as a known renal Hatchmore Labs GmbH

[0254] and / or liver insufficiency (and possibly its extent or stages), indications of missing enzymes, enzyme defects, allergies, etc., or consist of these.

[0255] In some embodiments, the individual physiological parameters include, for example, weight, gender, body mass index, and / or information about the patient's genotype, or consist of these.

[0256] In some embodiments, the system further comprises a dosage form of the drug. The drug, or its dosage form, is optionally located, for example, next to or in addition to a computer system (or data processing device) or other components of the system, which are usually interconnected or have signal links. A comprehensive evaluation of a large proportion of approved drugs with regard to their dosage regimens, side effect profiles, the number and severity of side effects, the dropout rate in clinical trials due to side effects, and the complexity of their dosage instructions, conducted by the inventors, revealed that drugs from certain drug classes are more difficult to dose than others. The system according to the invention is therefore particularly advantageous for these drug classes and drugs that are difficult to administer, since, for example, it allows for the precise dosing of the drug.This makes it possible to treat even patients with the aforementioned problematic drugs who would not be treatable using the standard therapy specified in the package insert, e.g. because they would suffer from excessively severe side effects.

[0257] In some embodiments, the system therefore has a dosage form of the drug, wherein the drug is a drug selected from the group consisting of ATC classes A, B, C, D, G, H, J, L, N, R, S and V, in particular from the group consisting of ATC classes B, C, L or N, and most preferably from the group consisting of ATC classes L and N.

[0258] If the medicinal product is an ATC class A medicinal product, it is preferably a medicinal product selected from the group consisting of ATC classes A03, A05, A07, A08, A10 and A16, in particular selected from the group consisting of ATC classes A08, A10 and A16, e.g. selected from the group consisting of ATC classes A08A, A10B and A16A.

[0259] If the medicinal product is a medicinal product of ATC class B, it is preferably a medicinal product selected from the group consisting of ATC classes B01, B02, B03 and B05, in particular selected from the group consisting of ATC classes B02 and B03, e.g. selected from the group consisting of ATC classes B01A, B02B and B03X.

[0260] If the medicinal product is a medicinal product of ATC class C, it is preferably a medicinal product selected from the group consisting of ATC classes C01, C02, C03, C07, C09 and C10, in particular selected from the group consisting of ATC classes C01, C02, C07, C09 and C10, especially preferably selected from the group consisting of ATC classes C09 and C10, e.g. selected from the group consisting of ATC classes C02K, C10A and C10B.

[0261] If the medicinal product is a medicinal product of ATC class D, it is preferably a medicinal product selected from the group consisting of ATC classes D07 and D11, in particular a medicinal product of ATC class D07, e.g. from ATC class D07A.

[0262] If the medicinal product is a drug from ATC class G, it is preferably a drug selected from the group consisting of ATC classes G01 and G03.

[0263] If the medicinal product is a drug from ATC class H, it is preferably a drug selected from the group consisting of ATC classes H01, H03 and H05, e.g. selected from the group consisting of ATC classes H01A, H01C, H03A and H05B. Hatchmore Labs GmbH

[0264] If the medicinal product is a medicinal product of ATC class J, it is preferably a medicinal product selected from the group consisting of ATC classes J01 and J05, in particular from ATC class J01G.

[0265] If the medicinal product is a medicinal product of ATC class L, it is preferably selected from the group consisting of ATC classes L01, L02, L03 and L04, in particular selected from the group consisting of ATC classes L01 and L04, e.g. selected from the group consisting of ATC classes L01B, L01E, L01F, L01X and L04A. If the medicinal product is a medicinal product of ATC class N, it is preferably selected from the group consisting of ATC classes N01, N02, N03, N05 and N06, in particular selected from the group consisting of ATC classes N03, N05 and N06, e.g. selected from the group consisting of ATC classes N03A, N05A, N05B, N06A and N06B.

[0266] If the medicinal product is an ATC class R medicinal product, it is preferably a medicinal product selected from the group consisting of ATC classes R01, R03, R05 and R07.

[0267] If the medicinal product is an ATC class S medicinal product, it is preferably a medicinal product selected from the group consisting of ATC classes S01 and S02.

[0268] If the drug is a drug from ATC class V, it is preferably a drug from ATC class V03, e.g., a drug from ATC class V03A. Antidotes are particularly difficult to individualize in dosage because their optimal therapeutic concentration often depends on the usually unknown amount of the ingested toxin. Therefore, if the drug is a drug from ATC class V03, it is preferably a drug from ATC class V03AB.

[0269] The inventors' evaluation of a large proportion of approved drugs with regard to their dosage regimens, side effect profiles, the number and severity of side effects, the dropout rate in clinical trials due to side effects, and the complexity of their dosing instructions, also revealed that drugs interacting with certain classes of drug targets, and especially with certain individual drug targets, are more difficult to dose than others. The system according to the invention is therefore particularly advantageous for these drugs that interact with difficult drug targets, as it makes it possible, for example, to treat even patients with the aforementioned problematic drugs who would be suboptimal or even untreatable using the standard therapy specified in the package insert, e.g., because they would suffer from excessively severe side effects.In some embodiments, the system therefore has a dosage form of the drug, wherein the drug interacts with a drug target and the drug target is selected from the group consisting of enzymes, receptors, transporters, ion channels, structural proteins, binding proteins, regulatory proteins, proteins of the immune system, proteins of the blood coagulation cascade and cell adhesion proteins, in particular from the group consisting of enzymes, receptors, transporters and ion channels.

[0270] If the drug target is an enzyme, it is preferably an enzyme selected from the group consisting of oxidoreductases, transferases and hydrolases.

[0271] If the drug target is an oxidoreductase, it is preferably an enzyme selected from the group consisting of the cytochrome P450 family, non-Cyp dehydrogenases, oxidases, reductases, oxygenases, and peroxidases, in particular selected from the group consisting of the cytochrome P450 family, non-Cyp dehydrogenases, reductases, and oxygenases. Specifically, a drug target may be selected from the group consisting of P08684, P11712, P10635, P20815, P33261, P10632, P05177, and P20813.

[0272] If the drug target is a transferase, it is preferably an enzyme selected from the group consisting of kinases, glycosyltransferases, such as Q16739, methyltransferases, acyltransferases, glutathione S-transferases, sulfotransferases, polymerases and others. Hatchmore Labs GmbH

[0273] Transferases, in particular selected from the group consisting of kinases and glutathione S-transferases, in particular a kinase. In particular, a kinase may be selected from the group consisting of P00519, 060674, P23458 and P52333. In particular, a glutathione S-transferase may be selected from the group consisting of P09211, P09488 and P30711.

[0274] If the drug target is a hydrolase, it is preferably an enzyme selected from the group consisting of esterases, glycosidases, peptidases / proteases, deaminases, deacetylases, ATPases, and other hydrolases, in particular selected from the group consisting of peptidases / proteases, esterases, and deacetylases, and in particular, it is a peptidase / protease. In particular, a peptidase / protease may be selected from the group consisting of P27487, P28074, P08246, and Q8NBP7. In particular, an esterase may be selected from the group consisting of P06276, P23141, and Q6LAP9.

[0275] If the drug target is a receptor, it is preferably a receptor selected from the group consisting of G protein-coupled receptors, receptor tyrosine kinases, ligand-gated ion channels, nuclear receptors, cytokine and growth factor receptors, Fc receptors and other receptors, in particular selected from the group consisting of G protein-coupled receptors, receptor tyrosine kinases, ligand-gated ion channels and nuclear receptors.

[0276] If the drug target is a G-protein-coupled receptor, it is preferably selected from the group consisting of amine receptors, peptide receptors, prostanoid receptors, nucleotide receptors, lipid receptors, and other G-protein-coupled receptors, particularly selected from the group consisting of amine receptors and peptide receptors. Specifically, a G-protein-coupled receptor may be selected from the group consisting of Q9H3N8, P21453, P30988, 060894, 060895, 060896, and Q9H228.

[0277] If the drug target is a receptor tyrosine kinase, it is preferably selected from the group consisting of P35968, P10721, P36888, P00533, P17948, P35916, P04626, P11362, P07949, P08581 and Q16620, and in particular selected from the group consisting of P35968, P10721, P36888, P00533 and P17948.

[0278] If the drug target is a transporter, it is preferably a transporter selected from the group consisting of ABC transporters, SLC transporters, and other membrane transporters. If the drug target is an ABC transporter, it may in particular be selected from the group consisting of P08183, Q9UNQ0, Q92887, 095342, P33527, Q5T3U5, 015439, 015438, and Q2M3G0.

[0279] If the drug target is an SLC transporter, it is preferably an SLC transporter selected from the group consisting of organic anion / cation / drug transporters, neurotransmitter transporters, glucose transporters, sodium / glucose transporters, nucleoside / nucleobase transporters, amino acid transporters, monocarboxylate transporters, peptide transporters, ion co-transporters, and bile acid transporters, and in particular selected from the group consisting of organic anion / cation / drug transporters and neurotransmitter transporters. If the drug target is an SLC transporter, a drug target may in particular be selected from the group consisting of Q9Y6L6, Q9NPD5, 015244, Q96FL8, Q86VL8, Q8TCC7, P23975, P31645, Q4U2R8, 015245, P46721, 094956 and 075751. If the drug target is an ion channel, it is preferably an ion channel selected from the group consisting of ligand-gated ion channels, voltage-gated ion channels and other ion channels.

[0280] If the drug target is a ligand-gated ion channel, it is preferably a ligand-gated ion channel selected from the group consisting of gamma-aminobutyric acid receptors, serotonin receptors, glutamate receptors, and acetylcholine receptors. Hatchmore Labs GmbH

[0281] If the drug target is a ligand-gated ion channel, a drug target may in particular be selected from the group consisting of P14867, P34903, P47869, P31644, Q99928, P18507, Q8N1C3, P46098, P48169, Q16445, P18505, 000591, 014764, P28472, P47870, P78334, Q9UN88, Q05586, Q13224, Q8TCU5, 015399, 060391, P36544, P43681, Q12879 and Q14957.

[0282] If the drug target is a voltage-gated ion channel, it is preferably a voltage-gated ion channel selected from the group consisting of voltage-gated sodium channels, voltage-gated potassium channels, and voltage-gated calcium channels. If the drug target is a voltage-gated ion channel, a drug target may in particular be selected from the group consisting of Q14524, Q9UI33, Q12809, Q15858, Q9NY46, P35498, P35499, Q99250, Q9Y5Y9, Q9UQD0, Q01118, Q00975, and Q13936.

[0283] If the drug target is a structural protein, it is preferably a structural protein selected from the group consisting of cytoskeletal proteins, extracellular matrix proteins, and other structural proteins. If the drug target is a cytoskeletal protein, it may in particular be a drug target selected from the group consisting of Q9H4B7 and P07437. If the drug target is a binding protein, it is preferably a binding protein selected from the group consisting of circulatory or extracellular transport proteins, intracellular calcium-binding proteins, chaperones or heat shock proteins, lectins, lipid-binding proteins, and nucleic acid-binding proteins.

[0284] If the drug target is a transport protein of the bloodstream or the extracellular space, a drug target may in particular be selected from the group consisting of P02768, P02763, P19652, P05543, P04278 and P08185.

[0285] If the drug target is an intracellular calcium-binding protein, a drug target may in particular be selected from the group consisting of P04083, P0DP23, P0DP24, P0DP25, P27797, P27824, P49069 and Q96LZ3.

[0286] If the drug target is a chaperone or heatshock protein, the drug target is specifically P11021.

[0287] If the drug target is a lectin, the drug target is specifically P49257.

[0288] If the drug target is a protein of the immune system, it is preferably a protein of the complement system, a cytokine, or a CD antigen.

[0289] If the drug target is a protein of the complement system, a drug target may in particular be selected from the group consisting of P02745, P02746, P02747, P01024, P0C0L4, P0C0L5 and P01031.

[0290] If the drug target is a CD antigen, a drug target may in particular be selected from the group consisting of P08183, Q9UNQ0, P35968, P10721, P36888, P16234, P04626, P09619, P11362, P21802, P22607, P19235, Q02763, Q9UM73, P12314, P08637, 075015, P12318, P31994, P31995, P21453, Q99062, Q92854 and P07333.

[0291] If the drug target is a cytokine, a drug target may in particular be selected from the group consisting of P01583, P01584, P01375, P05231, Q16552 and P05112.

[0292] If the drug target is a protein of the blood coagulation cascade, a drug target may in particular be selected from the group consisting of P00742, P00451, P00734, P04275, P00740, P08709, P03951, P12259, P00488, P04070 and P20043.

[0293] If the drug target is a cell adhesion protein, it is preferably an integrin, a cadherin, or a cell adhesion molecule from the immunoglobulin superfamily. Hatchmore Labs GmbH

[0294] If the drug target is an integrin, a drug target may in particular be selected from the group consisting of P20701, P05106 and P06756.

[0295] If the drug target is a cadherin, a drug target may in particular be selected from the group consisting of P33151, P12830, P19022, P22223 and P07949.

[0296] If the drug target is a cell adhesion molecule from the immunoglobulin superfamily, a drug target may in particular be selected from the group consisting of P13591, P05362 and P19320.

[0297] The inventors' evaluation of all approved drugs with regard to their side effect profiles, the severity of side effects, the dropout rate in clinical trials, and the complexity of their dosing instructions also revealed that dose finding is more difficult for certain drug targets than for others. The system according to the invention is therefore particularly advantageous for drugs that interact with these challenging drug targets, as it makes it possible, for example, to treat even patients with drugs that interact with the aforementioned problematic drug targets who would be untreatable using the standard therapy specified in the package insert, e.g., because they would suffer from excessively severe side effects.

[0298] Criteria for identifying difficult drug targets included two or more different drugs acting on the drug target, and whose dosing regimens or scientific literature indicated that particular problems arose in determining the optimal dose and / or dosing regimen. Such indications included, for example, references to drug dose titration, references to a narrow therapeutic index, or references to strong, dose-dependent side effects, to name just a few.

[0299] In this way, the following preferred drug targets were identified, which are listed below along with one of their indications:

[0300] P00533 [UniProt ID], for the treatment of cancer.

[0301] P01375 [UniProt ID], for the treatment of an autoimmune disease.

[0302] P04626 [UniProt ID], for the treatment of cancer.

[0303] P15692 [UniProt ID], for the treatment of cancer and / or macular degeneration.

[0304] P00519 [UniProt ID], for the treatment of cancer.

[0305] P11836 [UniProt ID], for the treatment of cancer and / or an autoimmune disease.

[0306] Q15116 [UniProt ID], for the treatment of cancer.

[0307] P16410 [UniProt ID], for the treatment of cancer.

[0308] P07550 [UniProt ID], for the treatment of an (obstructive) respiratory disease. P07437 [UniProt ID], for the treatment of cancer.

[0309] P00451 [UniProt ID], for the treatment of hemophilia.

[0310] P00734 [UniProt ID], for the treatment of hemophilia.

[0311] P04150 [UniProt ID], for the treatment of an immune system disorder.

[0312] P04818 [UniProt ID], for the treatment of cancer.

[0313] P08581 [UniProt ID], for the treatment of cancer.

[0314] P08588 [UniProt ID], for the treatment of high blood pressure.

[0315] P09874 [UniProt ID], for the treatment of cancer.

[0316] P10827 [UniProt ID], for the treatment of a hormonal disorder.

[0317] P11802 [UniProt ID], for the treatment of cancer.

[0318] P14416 [UniProt ID], for the treatment of a mental disorder, especially for the treatment of anxiety, depression, psychosis and / or schizophrenia.

[0319] P14867 [UniProt ID], for the treatment of epilepsy and / or a mental disorder, especially for the treatment of anxiety, depression, psychosis and / or schizophrenia.

[0320] P15056 [UniProt ID], for the treatment of cancer.

[0321] P23458 [UniProt ID], for the treatment of an autoimmune disease. Hatchmore Labs GmbH

[0322] P28223 [UniProt ID], for the treatment of mental disorders, in particular anxiety, depression, psychosis and / or schizophrenia. P30556 [UniProt ID], for the treatment of high blood pressure, coronary artery disease, post-myocardial infarction, migraine and / or chronic kidney disease.

[0323] P31639 [UniProt ID], for lowering blood sugar levels.

[0324] P31645 [UniProt ID], for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0325] P35372 [UniProt ID], for the treatment of a disease of the nervous system and / or for the treatment of pain.

[0326] P35498 [UniProt ID], for the treatment of epilepsy.

[0327] P35968 [UniProt ID], for the treatment of cancer.

[0328] P36888 [UniProt ID], for the treatment of cancer.

[0329] P42345 [UniProt ID], for the treatment of cancer.

[0330] P43119 [UniProt ID], for the treatment of pulmonary (arterial) hypertension.

[0331] Q01959 [UniProt ID], for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0332] Q02750 [UniProt ID], for the treatment of cancer.

[0333] Q06187 [UniProt ID], for the treatment of cancer.

[0334] Q7L0J3 [UniProt ID], for the treatment of epilepsy.

[0335] Q96SW2 [UniProt ID], for the treatment of cancer.

[0336] Q9GZT9 [UniProt ID], for the treatment of anemia.

[0337] Q9UM73 [UniProt ID], for the treatment of cancer.

[0338] 000329 [UniProt ID], for the treatment of cancer.

[0339] 075874 [UniProt ID], for the treatment of cancer.

[0340] P00374 [UniProt ID], for the treatment of cancer and / or for the treatment of an autoimmune disease.

[0341] P00742 [UniProt ID], for the treatment and / or prophylaxis of thrombosis.

[0342] P01008 [UniProt ID], for the treatment and / or prophylaxis of thrombosis.

[0343] P01116 [UniProt ID], for the treatment of cancer.

[0344] P03372 [UniProt ID], for the treatment of cancer.

[0345] P04035 [UniProt ID], for the treatment of hypercholesterolemia.

[0346] P04629 [UniProt ID], for the treatment of cancer.

[0347] P06401 [UniProt ID], for the prevention of pregnancy in women.

[0348] P07949 [UniProt ID], for the treatment of cancer.

[0349] P08235 [UniProt ID], to increase urine production.

[0350] P08908 [UniProt ID], for the treatment of depression.

[0351] P10275 [UniProt ID], for the treatment of cancer.

[0352] P10276 [UniProt ID], for the treatment of a skin condition.

[0353] P10415 [UniProt ID], for the treatment of cancer.

[0354] P10721 [UniProt ID], for the treatment of cancer.

[0355] P11229 [UniProt ID], for the treatment of a disorder of the digestive tract and / or a disorder of bladder function.

[0356] P11362 [UniProt ID], for the treatment of cancer.

[0357] P11388 [UniProt ID], for the treatment of cancer.

[0358] P11473 [UniProt ID], for the treatment of a systemic hormonal disorder.

[0359] P12821 [UniProt ID], for the treatment of high blood pressure, for the treatment of coronary artery disease, for the treatment of the condition following a heart attack, for the treatment of migraine and / or for the treatment of chronic kidney disease.

[0360] P14324 [UniProt ID], for the treatment of osteoporosis.

[0361] P20309 [UniProt ID], for the treatment of an obstructive airway disease.

[0362] P20711 [UniProt ID], for the treatment of a disease of the nervous system.

[0363] P20839 [UniProt ID], for the treatment of autoimmune diseases or to prevent organ rejection during organ transplantation.

[0364] P21453 [UniProt ID], for the treatment of epilepsy.

[0365] P21554 [UniProt ID], for the treatment of cancer.

[0366] P21964 [UniProt ID], for the treatment of a disease of the nervous system. Hatchmore Labs GmbH

[0367] P22303 [UniProt ID], for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0368] P23219 [UniProt ID], for the treatment of pain and / or inflammation.

[0369] P23921 [UniProt ID], for the treatment of cancer.

[0370] P23975 [UniProt ID], for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0371] P25101 [UniProt ID], for the treatment of hypertension, especially for the treatment of pulmonary arterial hypertension.

[0372] P27815 [UniProt ID], for the treatment of an autoimmune disease.

[0373] P28222 [UniProt ID], for the treatment of headaches.

[0374] P30518 [UniProt ID], to increase urine production.

[0375] P30874 [UniProt ID], for the treatment of a systemic hormonal disorder.

[0376] P35348 [UniProt ID], for the treatment of a urological condition.

[0377] P35354 [UniProt ID], for the treatment of pain and / or inflammation.

[0378] P35367 [UniProt ID], for the treatment of allergic reactions.

[0379] P40238 [UniProt ID], for the treatment and / or prophylaxis of bleeding.

[0380] P41145 [UniProt ID], for the treatment of pruritus.

[0381] P41180 [UniProt ID], for the treatment of a hormonal disorder affecting parathyroid hormones.

[0382] P42336 [UniProt ID], for the treatment of cancer.

[0383] P61073 [UniProt ID], for the mobilization of hematopoietic stem cells into the blood. Q02108 [UniProt ID], for the treatment of a cardiovascular disease. Q03431 [UniProt ID], for the treatment of a hormonal disorder affecting parathyroid hormones.

[0384] Q05586 [UniProt ID], for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0385] Q05940 [UniProt ID], for the treatment of a disease of the nervous system.

[0386] Q08209 [UniProt ID], for the treatment of an autoimmune disease.

[0387] Q13547 [UniProt ID], for the treatment of cancer.

[0388] Q13936 [UniProt ID], for the treatment of a cardiovascular disease. Q14524 [UniProt ID], for the treatment of a cardiovascular disease. Q15116 [UniProt ID], for the treatment of cancer.

[0389] Q16236 [UniProt ID], for the treatment of an autoimmune disease.

[0390] Q99835 [UniProt ID], for the treatment of cancer.

[0391] Q9BQB6 [UniProt ID], for the treatment and / or prophylaxis of thrombosis.

[0392] P08069 [UniProt ID], for the treatment of cancer.

[0393] P08913 [UniProt ID], for the treatment of hypertension or for stimulating the activity of the central nervous system, especially to increase concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[0394] P07766 [UniProt ID], for the treatment of cancer or for the treatment of an autoimmune disease.

[0395] P43220 [UniProt ID], for the treatment of diabetes.

[0396] Q9NZQ7 [UniProt ID], for the treatment of cancer.

[0397] P15391 [UniProt ID], for the treatment of cancer.

[0398] Q02223 [UniProt ID], for the treatment of cancer.

[0399] P06213 [UniProt ID], for the treatment of diabetes.

[0400] Q07011 [UniProt ID], for the treatment of cancer.

[0401] Q04609 [UniProt ID], for the treatment of cancer.

[0402] P56856 [UniProt ID], for the treatment of cancer.

[0403] Q08722 [UniProt ID], for the treatment of cancer.

[0404] P68871 [UniProt ID], for the treatment of anemia.

[0405] Q9UBS5 [UniProt ID], for cataplexy or narcolepsy, or as a muscle relaxant.

[0406] P07477 [UniProt ID], for the treatment of a disease of the digestive tract, especially for the treatment of pancreatitis. Hatchmore Labs GmbH

[0407] Q12908 [UniProt ID], for the treatment of a disease of the digestive tract or a metabolic disorder.

[0408] P00441 [UniProt ID], for the treatment of a disease of the nervous system.

[0409] P17181 [UniProt ID], for the treatment of an autoimmune disease.

[0410] P16233 [UniProt ID], for the treatment of a disease of the nervous system or a disease of the digestive tract.

[0411] P25092 [UniProt ID], for the treatment of a disease of the digestive tract.

[0412] P10747 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0413] P25942 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0414] P43489 [UniProt ID] for the treatment of an autoimmune disease.

[0415] Q9Y5U5 [UniProt ID] for the treatment of cancer.

[0416] P01589 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0417] P08887 [UniProt ID] for the treatment of an autoimmune disease.

[0418] P05231 [UniProt ID] for the treatment of an autoimmune disease.

[0419] P31358 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0420] P16422 [UniProt ID] for the treatment of cancer.

[0421] P04626 [UniProt ID] for the treatment of cancer.

[0422] P01137 [UniProt ID] for the treatment of cancer.

[0423] 000206 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease or for the treatment of a neurodegenerative disease.

[0424] Q9NR96 [UniProt ID] for the treatment of cancer, autoimmune disease, or infectious disease.

[0425] P55899 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0426] P17948 [UniProt ID] for the treatment of cancer or for the treatment of a neurodegenerative disease.

[0427] P49763 [UniProt ID] for the treatment of cancer.

[0428] P17931 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0429] Q9UQD0 [UniProt ID] for the treatment of an autoimmune disease.

[0430] 014788 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0431] P01024 [UniProt ID] for the treatment of an autoimmune disease.

[0432] P49770 [UniProt ID] for the treatment of an eye disease.

[0433] 043915 [UniProt ID] for the treatment of an eye disease.

[0434] 095390 [UniProt ID] for the treatment of anemia.

[0435] P61812 [UniProt ID] for the treatment of cancer or for the treatment of fibrosis.

[0436] P10600 [UniProt ID] for the treatment of cancer or for the treatment of fibrosis.

[0437] Q13705 [UniProt ID] for the treatment of a disease of the cardiovascular system or for the treatment of a disease of the musculoskeletal system.

[0438] P27037 [UniProt ID] for the treatment of a disease of the cardiovascular system or for the treatment of a disease of the musculoskeletal system.

[0439] P20138 [UniProt ID] for the treatment of cancer.

[0440] P28908 [UniProt ID] for the treatment of cancer.

[0441] P20273 [UniProt ID] for the treatment of cancer.

[0442] P40259 [UniProt ID] for the treatment of cancer.

[0443] Q96NY8 [UniProt ID] for the treatment of cancer.

[0444] P09758 [UniProt ID] for the treatment of cancer.

[0445] P13726 [UniProt ID] for the treatment of cancer.

[0446] P15328 [UniProt ID] for the treatment of cancer.

[0447] P22223 [UniProt ID] for the treatment of cancer.

[0448] P49765 [UniProt ID] for the treatment of cancer.

[0449] P49767 [UniProt ID] for the treatment of cancer. Hatchmore Labs GmbH

[0450] Q9Y275 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0451] 075888 [UniProt ID] for the treatment of cancer or for the treatment of an autoimmune disease.

[0452] P06731 [UniProt ID] for the treatment of cancer.

[0453] P26951 [UniProt ID] for the treatment of cancer.

[0454] Q5ZPR3 [UniProt ID] for the treatment of cancer.

[0455] P32970 [UniProt ID] for the treatment of cancer.

[0456] Q9NYJ7 [UniProt ID] for the treatment of cancer

[0457] P24394 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of atopic dermatitis.

[0458] P29460 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of psoriasis.

[0459] Q9NPF7 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of psoriasis.

[0460] P28907 [UniProt ID] for the treatment of cancer.

[0461] Q16552 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of psoriasis.

[0462] P26010 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of Crohn's disease.

[0463] P01031 [UniProt ID] for the treatment of an autoimmune disease, in particular for the reduction of overactivation of the complement system.

[0464] PODOX4 [UniProt ID] for the treatment of an autoimmune disease.

[0465] P05113 [ÜniProt ID] for the treatment of an autoimmune disease, especially for the treatment of asthma.

[0466] Q8NB78 [UniProt ID] for the treatment of a cardiovascular disease. P13612 [ÜniProt ID] for the treatment of an autoimmune disease, in particular multiple sclerosis.

[0467] Q13421 [UniProt ID] for the treatment of cancer.

[0468] P80404 [UniProt ID] for the treatment of a disease of the nervous system.

[0469] P30542 [UniProt ID] for the treatment of a disease of the nervous system or for the treatment of cancer.

[0470] P25705 [UniProt ID] for the treatment of mitochondrial dysfunction or cancer.

[0471] Q9Y3Q4 [UniProt ID] for the treatment of a disease of the cardiovascular system, especially for the treatment of heart failure.

[0472] Q8NBP7 [UniProt ID] for the treatment of a disease of the cardiovascular system, especially for the treatment of hypercholesterolemia.

[0473] Q9NQ25 [UniProt ID] for the treatment of cancer.

[0474] P18405 [ÜniProt ID] for the treatment of a disease of the urinary system, in particular for the treatment of benign prostatic hyperplasia.

[0475] P29597 [UniProt ID] for the treatment of an autoimmune disease, especially for the treatment of psoriasis.

[0476] Q9BQB4 [Uniprot ID] for the treatment of a bone disease.

[0477] In some embodiments, the system further features several dosage forms of the drug with different, preferably discrete, dose options.

[0478] In some embodiments, "discrete dose options" refer to the dosage strengths offered for a treatment, such as the approved dosage forms of a drug. For example, the drug Levothyroxine / Tirosint from IBSA INSTITUT BIOCHIMIQUE SA is approved in the USA in the form of capsules containing 0.013 mg, 0.025 mg, 0.0375 mg, 0.044 mg, 0.05 mg, 0.0625 mg, 0.075 mg, 0.088 mg, 0.1 mg, 0.112 mg, 0.125 mg, 0.137 mg, 0.15 mg, 0.175 mg, and 0.2 mg of the levothyroxine sodium salt, which corresponds to 15 discrete dose options in this example.

[0479] A dosage option can be, for example, a tablet, a capsule, a powder, a solution, a suspension, an injection, or any other dosage form. The system can therefore include, for example, a vial containing the drug and a blister pack of tablets containing the same drug. Hatchmore Labs GmbH

[0480] Alternatively or additionally, in some embodiments, two dosage options of a drug may also differ in their concentration or quantity. For example, a first dosage option of the drug may be a tablet containing 200 mg of the active ingredient, while a second dosage option of the same drug may be a tablet containing 500 mg of the same active ingredient.

[0481] The system can therefore include, in addition to, for example, a computer system with data storage and other components, a drug that is available in different dosage options, e.g., in the form of two blisters with tablets containing the same drug, where, for example, the amount of active ingredient in the tablets of the first blister differs from the amount of active ingredient in the tablets of the second blister.

[0482] In some embodiments, determining includes calculating, looking up or reading, each from a storage medium, the dose of the next dosage form to be administered to the patient, or consists thereof.

[0483] In some embodiments, determining includes or consists of calculating the time of administration of the next dosage form.

[0484] In some embodiments of the system, the output device (as an information output device for displaying information) visually, audibly, and / or haptically displays, or is configured to display, the determined time and / or dose of the next dosage form of the drug on at least one device. Alternatively, it is prepared for signal transmission to a device and can be controlled accordingly by the system or its control device so that the aforementioned information can be displayed there. In certain embodiments, the device may be included in the system, while in others it may not.

[0485] In some embodiments, the device may be or include a monitor, a display, a computer, a laptop, a tablet, an e-reader, a personal assistant, a comprehensive AI device, a smartphone, a wearable, a smartwatch, smart glasses, a sensor, or a speaker.

[0486] In some embodiments of the system, the feedback device is configured to record patient data relating to the timing of the feedback or the timing of the patient's response to the administration of a dosage form of the drug.

[0487] In some embodiments, the feedback device is configured to collect patient data relating to the nature of the patient's response to the administration of a dosage form of the drug.

[0488] The "nature of response" of a patient to the administration of a dosage form of a drug can, for example, express an insufficient drug effect, a satisfactory drug effect, an adverse drug effect such as insufficient drug tolerance, or satisfactory drug tolerance. In certain formulations, this nature of the patient's response may be, or include, the point at which the patient requests or demands a further dose.

[0489] In some embodiments, the feedback device is configured to collect patient data regarding the drug's effect.

[0490] In some implementations, the patient data concerning the drug effect includes the time of insufficient drug response, in particular the time of onset of insufficient drug response. This time can, for example, be entered by the patient. Hatchmore Labs GmbH

[0491] In some embodiments, the time of insufficient drug response (ttttttttttttttttttttttttttttttttttttttttttttttttttttttttt in the patient is understood as the time at which the patient notices symptoms of insufficient drug response in himself / herself and / or at which a third party, such as a treating physician or nurse, notices symptoms of insufficient drug response in the patient.

[0492] The time of insufficient drug effect may differ from the time of detection of the insufficient drug effect, for example by input via the feedback device or by other means.

[0493] In some embodiments, the patient data concerning the drug effect includes the time of a satisfactory drug effect, in particular the time of onset of a satisfactory drug effect. This time can also be specified or entered by the patient, for example.

[0494] In some embodiments, the point in time (tzAMw) of a satisfactory drug effect (ZAMW) is understood to be the point in time at which the patient notices a satisfactory drug effect in himself and / or at which a third party, such as a treating physician or nurse, notices a satisfactory drug effect in the patient.

[0495] The time of satisfactory drug effect may differ from the time of detection, for example, by input via the feedback device or by other means. The same applies to the time (tuMv) of insufficient drug tolerance, which in some embodiments is understood as the time at which the patient notices symptoms of insufficient drug tolerance and / or at which a third party, such as a treating physician or nurse, notices symptoms of insufficient drug tolerance in the patient, as well as to the time (tzMv) of satisfactory drug tolerance, which in some embodiments is understood as the time at which the patient determines satisfactory drug tolerance and / or at which a third party, such as a treating physician or nurse, determines satisfactory drug tolerance in the patient.

[0496] In some embodiments, the system's feedback device is configured to record patient data concerning drug tolerance. For this purpose, it can be configured, for example, as a dedicated input field on a touchscreen display, form, etc., associated with the feedback device. This input field preferably only accepts entries in the expected format (similar to "dd.mm.yy" for entering a date and nothing else).

[0497] In some implementations, the patient data concerning drug tolerance includes the point in time when drug tolerance is insufficient. This point in time can also be indicated or entered by the patient, for example.

[0498] In some embodiments, the point in time (ttpv) of insufficient drug tolerance is understood to be the point in time at which the patient notices symptoms of insufficient drug tolerance in himself or a third party, such as a treating physician or nurse, notices symptoms of insufficient drug tolerance in the patient.

[0499] In some implementations, the patient data concerning drug tolerance includes the point in time when satisfactory drug tolerance is achieved. This point in time can also be specified or entered by the patient, for example.

[0500] In some formulations, the point in time (tTM) of satisfactory drug tolerance is understood to be the point in time at which the patient determines satisfactory drug tolerance in themselves and / or at which a third party, such as a treating physician or nurse, determines satisfactory drug tolerance in the patient. Hatchmore Labs GmbH

[0501] In some embodiments, the patient data captured by the feedback device is captured or read in by a person operating the feedback device and / or automatically by a device.

[0502] In some embodiments, the feedback device is configured to capture patient data when the patient operates the device. To ensure that the operation is performed by the patient and / or a physician, nurse, and / or caregiver authorized by the patient, some embodiments may require and employ identification verification, such as a personal numerical code, password, barcode, QR code, voice recognition, and / or biometrics, etc.

[0503] In some embodiments, the system includes or is connected to a device for (automatically) recording patient data. The device records, for example, blood pressure, temperature, blood glucose level, heart rate, blood oxygen saturation, respiratory rate, the electrical activity of an organ, the concentration of the drug in the urine, and / or the CO2 content of the patient's breath, and / or reads this type of data.

[0504] In some embodiments of the system, the feedback device, or some or all functional components of the feedback device, on the one hand, and the output device, on the other hand, are part of the same device or apparatus.

[0505] In some embodiments of the system, the electronic control device or some or all functional components of the electronic control device on the one hand and the data storage device on the other hand are part of the same device or apparatus.

[0506] In some embodiments of the system, the electronic control device, or some or all of its functional components, and the sensing device are part of the same device or apparatus. In some embodiments of the system, the output device, or some or all of its functional components, and the sensing device are part of the same device or apparatus.

[0507] In some embodiments of the system, the feedback device, or some or all of its functional components, and the sensing device are part of the same device or apparatus. In some embodiments of the system, the output device, the sensing device, and the feedback device, and / or their functional components, are part of the same device or apparatus.

[0508] In some embodiments, the system may include one, several, or all of the above-mentioned concepts, models, and / or patient-related data to generate dosing algorithms for all therapeutic areas, ranging from those with easily measurable endpoints that are highly predictive of and / or correlate with subsequent outcomes, to more complex cases that may require more invasive and / or costly procedures (e.g., tumor biopsies, scans) and / or repeated observations due to inherently variable measurements.

[0509] In some embodiments, the system can be used to create personalized dosing algorithms of increasing complexity. For example, one embodiment might be a simple target-based algorithm based on aggregated endpoints, such as patient and / or physician ratings after each month. Another, more complex embodiment might include a dose-titration algorithm that uses multiple (objective) parameters, such as neutrophil counts or changes in tumor size. This could involve an individualized efficacy target, where the patient attempts to achieve their individual target value. Hatchmore Labs GmbH

[0510] to achieve the target as quickly as safety and / or tolerability allows. Alternatively, it could have an individual safety target that uses a less aggressive, more patient-friendly dosing algorithm.

[0511] The system according to the invention is preferably designed and suitable for individualizing the administration of a drug, for example, by adapting the administration pattern to the patient's specific response. In some embodiments, this is achieved by further programming the electronic control device in such a way that determining the time (tA) n ) and / or the dose (D n) the next dosage form of the drug to be administered to a patient (DFAMn) is determined by relating the patient data from the feedback device at at least one specific time point, or for that time point, to a determination, in particular calculation, of the concentration of the drug (cAM) and / or the active metabolite of the drug (cAMB) in a compartment of the patient's body for the same time point, carried out by the electronic control device on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage.

[0512] When the term "determining" is used herein, it may refer to the process or action by which the system described herein, and / or a part of the system, and / or one or more functional components and / or devices, arrive at a specific result, conclusion, or value through the application of one or more algorithms, computational procedures, measurements, analyses, or comparisons. This process may involve the processing of input data, the application of predefined rules or criteria, and the use of databases or reference values. "Determining" may be performed in real time or based on historical data to capture current states or predict future events.

[0513] When the term "determination" is used herein, it may refer to the result or outcome of a calculation and / or determination process generated by the system described herein and / or a part of the system and / or one or more functional components and / or devices. A determination may take the form of a numerical value, a qualitative assessment, a classification, or a decision. It represents the conclusion reached by the system based on the data, algorithms, and processing methods available to it. The determination may, among other things, serve as the basis for further actions, decisions, or calculations within the system or be transmitted to external systems or users for further use.

[0514] The control device is therefore preferably programmed to relate the time of occurrence of events that reflect individual pharmacodynamics to pharmacokinetic considerations for that time, such as time-dependent concentration calculations, and then, in response, determine the time and dose for the next drug administration and / or adjust patient-specific parameters stored in memory. Several examples of such individualized control are explained in more detail below.

[0515] Such individualized control of drug administration is particularly advantageous for drugs with complex pharmacokinetics. These drugs are often characterized by a large volume of distribution.

[0516] In some embodiments, the electronic control device is programmed to assume a volume of distribution in the patient's body of at least 0.15 l / kg for the drug (D) and / or the active metabolite of the drug (MB), such as a volume of distribution of at least 0.5 l / kg, or at least 0.8 l / kg, or at least 2.0 l / kg, or at least 10 l / kg.

[0517] Individualized control of drug administration is particularly advantageous for drugs characterized by low bioavailability, since in such cases Hatchmore Labs GmbH

[0518] Drugs often exhibit higher interindividual variability. In some embodiments, the electronic control device is therefore programmed to assume a bioavailability of at most 75% for the drug (D) and / or the active metabolite of the drug (MB), such as a bioavailability of at most 50%.

[0519] Individualized control of drug administration is particularly advantageous for drugs characterized by a short time-to-peak concentration, since the drug concentration in the body varies more significantly with such drugs, and there is often greater interindividual variability. In some embodiments, the electronic control device is therefore programmed to assume a time-to-peak concentration of no more than 6 hours (6h) for the drug (D) and / or the drug's active metabolite (AMB), such as no more than 2h or, in particular, no more than 1h.Individualized control of drug administration is particularly advantageous for drugs characterized by a short plasma half-life, since the drug concentration in the body varies more significantly with such drugs, and there is often greater interindividual variability. In some embodiments, the electronic control device is therefore programmed to assume a plasma half-life of no more than 6 hours for the drug (D) and / or its active metabolite (AMB), such as no more than 2 hours, and in particular no more than 1 hour.

[0520] Individualized control of drug administration is particularly advantageous for drugs characterized by high clearance, since the drug concentration in the body varies more significantly with such drugs, and there is often greater interindividual variability. In some embodiments, the electronic control device is therefore programmed to assume a clearance of at least 500 ml / min (based on a body weight of 70 kg) for the drug (D) and / or its active metabolite (MB), such as at least 700 ml / min, and in particular at least 900 ml / min.

[0521] The kinetics of drugs with complex pharmacokinetics often cannot be described by a simple one-compartment model. Therefore, in some embodiments, the electronic control device is advantageously programmed to assume a one-compartment model for the pharmacokinetics of the drug (cAM(t)) and / or the active metabolite of the drug (cAMB(t)), but preferably a two-compartment model, a three-compartment model, or a model with more than three compartments.

[0522] The term "one-compartment model" is used here to describe the simplest case in pharmacokinetics, where the concentration of a drug in the blood observed after intravenous administration can be described by a single, usually open, compartment model. This is the case, for example, when the drug mixes with the blood at the injection site, forming a so-called bolus that is continuously diluted by the flowing blood, and the drug is distributed very rapidly and evenly throughout the entire body. The entire body can then be considered a single compartment, and the pharmacokinetic data can be determined according to the so-called open one-compartment model.The concentration of the drug present in this compartment then depends on the administered dose and the size of the distribution space, and the rate of the drug concentration decrease in the compartment depends on the elimination constant.

[0523] A one-compartment model consists only of the central compartment and describes the body as a single, homogeneous compartment in which the drug is immediately distributed from this compartment. This model is described by:

[0524] C(t) = D / V* e A (-kt)

[0525] where "C(t)" is the drug concentration at time t, "D" is the dose, "V" is the volume of distribution, and "k" is the elimination rate constant. Hatchmore Labs GmbH

[0526] The term "two-compartment model" is used here to describe a common occurrence in pharmacokinetics where the plasma concentration of a drug observed after intravenous administration can be described by an open two-compartment model. This is the case, for example, when, after intravenous administration, the drug mixes very rapidly with the entire blood volume and quickly distributes to tissues with the highest perfusion (such as the brain, heart, liver, and kidneys), but less rapidly to tissues with lower perfusion (such as fat, skin, and muscles). Tissue membrane permeability, tissue mass, and solubility also play a role. The distribution of the drug to the different tissues is a complex process that can be simplified by postulating two distribution compartments.The so-called "central compartment" (with a first volume) represents, in addition to the blood, the organs that quickly reach equilibrium with the blood due to their high perfusion. In this model, all less well-perfused tissues, such as fat, skin, and muscle, are grouped into the "peripheral" or tissue compartment (with its own second volume). In this "two-compartment model," drug elimination occurs exclusively from the central compartment.

[0527] A two-compartment model divides the body into a central compartment (plasma and well-perfused tissue) and a peripheral compartment (poorly perfused tissue). Drug transfer occurs between these compartments. This model is described by:

[0528] C(t) = A * e A (-at) + B * e A (-ßt)

[0529] Where “A” is the y-intercept of the distribution phase (a phase), “B” is the y-intercept of the elimination phase (β phase), and “a” and “β” are hybrid rate constants representing distribution and elimination.

[0530] A "three-compartment model" or "multi-compartment model" is used here to describe a situation where the observed blood plasma concentrations of the drug after intravenous administration can no longer be described by a simpler compartment model. The physiological basis for this is the division of the body into several distribution compartments, such as, in the three-compartment model, the distribution compartments V1 (vascularly rich organs: blood, kidney, heart, liver, brain), V2 (muscle group), and V3 (fat and vascular-poor group), each with its own rate constants that describe the distribution kinetics between the individual compartments.

[0531] A three-compartment model adds a second peripheral compartment, typically representing tissues with slower drug distribution. This model is described by: C(t) = A * e A (-at) + B * e A (-ßt) + C * e A (-yt)

[0532] where “A” is the y-intercept of the fast distribution phase, “B” is the y-intercept of the slow distribution phase, “C” is the y-intercept of the elimination phase, and “a”, “ß” and “y” are the hybrid rate constants representing a fast distribution, a slow distribution and an elimination.

[0533] These models provide a framework for analyzing the absorption, distribution, metabolism and excretion of drugs, enabling more accurate predictions of drug behavior and dosing strategies.

[0534] The term "effect compartment" is preferably used herein to refer to the pharmacokinetic compartment that comprises the site of action of the drug or its active metabolite, i.e., the organ or group of cells whose function is or are to be affected by the drug, for example, by the drug binding to its pharmacological target there. In a one-compartment model, the effect compartment is one compartment of the model. In a two- or multi-compartment model, the effect compartment may be the central or the Hatchmore Labs GmbH

[0535] peripheral or a specific one of the peripheral compartments, and often in such a case it is the peripheral or a specific one of the peripheral compartments.

[0536] The effect compartment is a hypothetical compartment that can be added to any of these models to explain delayed drug response. It represents the site of drug action and is linked to the central compartment by a first-order rate constant (keO). The effect compartment allows for the modeling of the time lag between measured concentration and observed effect, often referred to as a hysteresis loop in the concentration-response curve.

[0537] The relationship between the concentration of the central compartment (C) and the concentration of the effect compartment (Ce) is described by the differential equation: dCe / dt = keO * (C - Ce)

[0538] where “keO” is the constant of the equilibration rate of the effect compartment. This approach allows the modeling of delayed drug responses without altering the underlying pharmacokinetic model and is therefore applicable to models with one, two, or three compartments.

[0539] Technical terms such as "central compartment" or "peripheral compartment" are used here in the sense customary for those skilled in the art. If the meaning of a term is unclear, the meaning given to that term in the book "Introduction to Pharmacokinetics" by Gugeler and Klotz (2000), 2nd edition, published by GOVI-Verlag, shall apply.

[0540] Particularly when, in a two- or multi-compartment model, the drug's effect does not occur in the central compartment, it is advantageous to relate the events that reflect individual pharmacodynamics to the individual pharmacokinetics in a compartment other than the central compartment. In some embodiments, the compartment for which the PK / PD relationship is determined, or in particular calculated, is not the central compartment. For example, it may be the peripheral compartment. In particular, it may be the effect compartment.

[0541] As already explained, in some embodiments of the invention, the control device is programmed to relate the time of occurrence of events that are expressions of individual pharmacodynamics to a determination, in particular a calculation, of the concentration of the drug (cAM) and / or the active metabolite of the drug (cAMB) in a compartment of the patient's body for the same time. Determining the concentration of the drug (cAM) in a compartment and / or the active metabolite of the drug (cAMB) in a compartment can, in some embodiments, be an estimate based on empirical values.

[0542] When the term “estimation” is used herein, it may refer to a process or the result of a process in which an approximate determination of an unknown parameter, quantity or value, such as the concentration of the drug (cAM) and / or the active metabolite of the drug (cAMB) in a compartment of the patient’s body is made on the basis of incomplete, uncertain or approximate information.

[0543] In some different versions of the system listed here, an estimate may include one and / or several of the following aspects in any combination:

[0544] a data basis, using available data that are directly or indirectly related to the quantity to be estimated;

[0545] a methodology in which statistical, mathematical or heuristic procedures are used to derive the estimated value;

[0546] A modeling approach that uses models to represent the relationships between known and unknown quantities; Hatchmore Labs GmbH

[0547] an uncertainty quantification, whereby the uncertainties associated with the estimate can be determined and / or specified, for example by confidence intervals or standard errors,

[0548] an iterative refinement, whereby a continuous improvement of the estimate can take place through the integration of new data or insights;

[0549] a plausibility check, in which the estimate is evaluated for its consistency with known domain knowledge or experience;

[0550] an adaptivity, whereby the estimation method is able to adapt to changing conditions or data structures; and / or

[0551] a robustness, whereby the estimation method exhibits resistance to outliers, noise, or faulty input data.

[0552] The estimate can include both deterministic and probabilistic elements and serves to enable informed decisions or to support further calculations and analyses in situations where an exact determination is not possible or practical.

[0553] When this text refers to "empirical values," it can represent a collection of empirically determined key figures, parameters, or benchmarks that can serve as a guide or starting point for calculations, models, or forecasts. These empirical values ​​can include, among other things, the implicit knowledge of experts acquired through years of practice and take the form of qualitative assessments or expert opinions.

[0554] In some embodiments of the system, empirical values ​​can be used as initial estimates, calibration parameters or plausibility checks to improve the predictive power and clinical relevance of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models.

[0555] Empirical data can be considered a complementary source to evidence-based study results, particularly in situations where controlled clinical trials are not feasible for ethical, practical, or economic reasons. Estimating the concentration of the drug (cAM) and / or its active metabolite (cAMB) in a compartment of the patient's body can be entirely sufficient, especially when pharmacokinetic population studies, such as those conducted during drug approval, have shown that the time course of drug concentrations (cAM) and / or its active metabolite (cAMB) after administration does not vary, or varies only minimally, between individuals.For example, in such a case, a sufficiently accurate prediction of the concentration profile over time can be made based on the empirical data collected in the approval studies.

[0556] However, it is often the case that the pharmacokinetics of an administered drug are more or less variable between individuals.

[0557] In some embodiments, determining the drug concentration (cAM) in a compartment and / or the concentration of the drug's active metabolite (cAMB) in a compartment therefore involves or includes a calculation of the drug concentration in a compartment (cAMeff) and / or the concentration of the drug's active metabolite in a compartment (cAMBetf) based on the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic, and / or pharmacokinetic data stored in the data storage. Such a calculation is possible, for example, because extensive pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic, and / or pharmacokinetic data, particularly data on the drug's pharmacokinetics and pharmacodynamics, are collected during clinical trials for drug approval.From such data, the expert can develop models in which the pharmacokinetic parameters (such as the number of compartments, bioavailability, blood plasma half-life and clearance) Hatchmore Labs GmbH.

[0558] should be chosen so that calculations based on the selected parameters yield results that correspond as closely as possible to the observed behavior of the drug in the body.

[0559] Such data, in particular the pharmacokinetic and / or pharmacodynamic parameters determined in population studies, can be stored in some embodiments, e.g., in the data storage. Based on this data, a person skilled in the art can calculate the concentration of the drug (cAM) in a compartment and / or the concentration of the active metabolite of the drug (cAMB) in a compartment.

[0560] In order to relate the patient data recorded by the feedback device at at least a specific time point, or for that time point, to a determination, in particular a calculation, of the concentration of the drug (cAM) and / or the active metabolite of the drug (cAMB) in a compartment of the patient's body for the same time point, performed by the electronic control device on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data memory, the electronic control device is programmed in some embodiments to read pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data from the data memory, which show a temporal course of the concentration of the drug (cAM). eto map the time course of the drug concentration (cAM) in the patient's body, and then to use this time course to determine the concentration of the drug (cAM). e ff(t)) the time (tAnmax) and / or the magnitude of the next maximum concentration of the drug (cAM) e to calculate ff(tAnmax)) in the compartment; and / or to determine the time course of the concentration of the drug's active metabolite (cAMB). e to map or calculate and / or represent ff(t)) in the patient's body, and then, based on this time course, the concentration of the active metabolite of the drug (cAMB). e ff(t)) the time (tAnmax-AMβ) and / or the magnitude of the next maximum concentration of the active metabolite of the drug (cAMB) eto calculate ff(tAnmax-AMB)) in the compartment, wherein in some embodiments the compartment for which the time-dependent concentration calculations are performed is not the central compartment, but the effect compartment, provided the two do not coincide. It is particularly advantageous to know the time and / or magnitude of the next concentration maximum after administration of a dosage form of the drug in order to be able to advantageously interpret a patient's response to the administration of a dosage form of the drug and to use the timing and nature of the patient's response as a control element to determine the time (tA). n ) and / or the dose (D n ) to determine the next dosage form of the drug to be administered to a patient (DFAMn).

[0561] For example, if a patient experiences an insufficient drug effect during the onset phase after medication administration—that is, at a time before the drug or its active metabolite has reached its time-dependent concentration maximum in the effect compartment—this may be expected and does not necessarily indicate that the drug was underdosed and therefore requires a higher dose at the next administration. In one embodiment, patient data concerning insufficient drug effect (UAMW) are therefore used when determining the time (tA). n ) and / or the dose (D n ) the next dosage form of the drug to be administered to a patient (DFAMn) is not taken into account if the time of its occurrence (tuAMw) is a time that is after the time (tA< n-i)) the administration of the last dosage form of the drug (DFAM(ni>), but before the time of the last maximum drug concentration (cAMeff(tA(ni)max)), and if, at that time, the drug concentration (cAMeff(tuAMw)) calculated on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store is less than the value of a predefined minimum effective concentration of the drug in the compartment, in particular less than the value of a predefined minimum therapeutically effective concentration of the drug (cAMeff / MiN) in the effect compartment. This is because the patient experiences an insufficient drug effect at a time when an insufficient drug effect is due to falling below the minimum effective concentration of the Hatchmore Labs GmbH

[0562] Since the drug's effect is predictable, in this preferred embodiment it is not necessary to react to patient feedback. Figure 4 illustrates an example of such control logic. In one embodiment, the electronic control device is programmed, when determining the next dosage form (DFAMn) to be administered to the patient, to determine it in such a way that the next maximum concentration of the drug in the compartment (cAM(tAnmax)) will not exceed a predetermined therapeutic maximum (cAMetf / MAx) stored in the data memory within the compartment, particularly in the effect compartment. This type of control advantageously minimizes and / or avoids undesirable drug effects.

[0563] As previously explained, after administration of a dosage form of the drug, the drug concentration in the blood initially rises, reaches a maximum, and then falls again. A similar concentration profile also occurs, albeit with a time lag, in an effect compartment, provided the blood and effect compartments do not coincide. A patient reaction occurring in the period after the next concentration maximum can also be used to determine the time point (tA). n ) and / or the dose (D n ) the next dosage form of the drug to be administered to a patient (DFAMn) may be relevant.

[0564] In one embodiment, the electronic control device is therefore programmed to read pharmacological, pharmacodynamic, pharmacogenetic, pharmacometric and / or pharmacokinetic data from the data storage, which depict a temporal course of the concentration of the drug (cAM(t)) in the patient's body, and then, based on these, to calculate the concentration (cAM(tA nmax + tx )) at a time point (tA nmax + tx ) in a compartment, in particular in the effect compartment, located after the next maximum (cAM(tAnmax)) of the concentration.

[0565] For example, in one embodiment the electronic control device can be programmed so that when determining the time (tA) n) the administration of the next dosage form of the drug to the patient, this is chosen so that, taking into account data stored in the data storage and a therapeutic minimum concentration (cAMeff / MiN) maintained in the data storage, at time (tA n ) the concentration (cAM(tA) n )) after a final maximum of the concentration (cAM(tA) <n-i))max) den Wert für die, z. B. im Datenspeicher, vorgehaltene therapeutisch wirksame Minimalkonzentration (cAMeff / MiN) im Kompartiment, insbesondere im Effektkompartiment, nicht unterschreitet.

[0566] According to this embodiment, the concentration of the drug, particularly in the effect compartment, should therefore be kept at a level that allows for a consistently sufficient drug effect, and the time of administration is chosen accordingly.

[0567] To achieve this, the electronic control device can, for example, be programmed so that when it is time to administer the next-but-one dosage form of the drug (DFAM), <n+i;) verschiedene diskrete Optionen für den Zeitpunkt der Verabreichung gibt (zum Beispiel die Optionen, das Arzneimittel morgens, mittags oder abends einzunehmen, wie z. B. zusammen mit dem Frühstück oder zusammen mit dem Mittagessen oder zusammen mit dem Abendessen), die etwa im Datenspeicher vorliegen können, diejenige Option (tAoPTioN) als Zeitpunkt (tA< n+i)) the next-but-one dosage form is selected for administration, which is latest after the time (tAn) of the next administration, but at which the concentration (cAM(tA) <n+i;) eine vorgegebenen therapeutisch wirksame Minimalkonzentration (cAMetr / MiN) immer noch nicht unterschreitet. Mit anderen Worten, in dieser Ausführungsform ist die Steuervorrichtung so programmiert, die Verabreichung der übernächsten möglichst lange hinauszuzögern, aber nicht so lange, dass eine, z. B. im Datenspeicher, vorgegebene therapeutisch wirksame Minimalkonzentration (cAMeff / MiN) unterschritten würde.

[0568] In another embodiment, the time (tA< n +i)) the next-but-one dosage form to be administered (DFAM) <n+i;) vorgegeben sein. Dann kann beim Ermitteln der Dosis (D n) the next dosage form of the drug to be administered to the patient (DFAMn), taking into account the data stored in the data storage and a Hatchmore Labs GmbH data storage

[0569] the therapeutically effective minimum concentration (cAMetr / MiN), the dose (D n ) the next dosage form of the drug (DFAMn) are determined such that the concentration of the drug (cAM(tA) <n+i;)) zum Zeitpunkt (tA< n+i)) the intended administration of the next-but-one dosage form (DFAM) <n+i;) nach einem nächsten Maximum (cAnmax) der Konzentration die vorgegebene therapeutisch wirksame Minimalkonzentration (cAMetr / MiN) nicht unterschreiten wird. Mit anderen Worten, in dieser Ausführungsform ist der Zeitpunkt für die Verabreichung der übernächsten Dosierungsform vorgegeben, und die Steuervorrichtung ist dann so programmiert, dass die Dosis der verabreichten nächsten Dosierungsform hoch genug gewählt wird, dass eine, z. B. im Datenspeicher, vorgegebene therapeutisch wirksame Minimalkonzentration (cAMeff / MiN) zum Zeitpunkt der Verabreichung der übernächsten Dosierungsform noch nicht unterschritten würde. Vorzugsweise wird aber die Dosis in einem solchen Fall nicht unnötig hoch gewählt.

[0570] In one embodiment, the electronic control device is therefore programmed such that, if the dosage forms of the drug (DFAM) are available as dosage forms with different discrete dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3), the dose option is selected with which the concentration (cAM(tA< n +i)) at time (tA< n +i)) the intended administration of the next-but-one dosage form (DFAM) <n+i;) nach einem nächsten Maximum (cAnmax) der Konzentration eine vorgegebene therapeutisch wirksame Minimalkonzentration (cAMetr / MiN) nicht unterschritten wird und die unter den Dosisoptionen, die diese Bedingung erfüllen, die geringste Dosis hat.

[0571] While a patient response indicating insufficient drug effect during the onset phase after administration of a dosage form of the drug often merely indicates that a therapeutically effective concentration in the effect compartment has not yet been reached, and is therefore ignored in some implementations, patient feedback indicating insufficient drug effect after reaching the maximum drug concentration in the effect compartment contains important information, particularly the time at which such a patient response occurred. For example, at such a time, the patient's individual minimum effective drug concentration in the effect compartment may have been undershot.

[0572] In one embodiment, the electronic control device is therefore programmed so that patient data concerning an insufficient drug effect (UAMW) is taken into account when determining the time (tA). n ) and / or the dose (D n ) the next dosage form of the drug to be administered to a patient (DFAMn) should be taken into account if the time of its occurrence (tuAMw) is a time that is after the time (tA< n -i)) the administration of the last dosage form of the drug, and after the time of the last maximum (tA(ni)max) of the concentration of the drug cAM.

[0573] This happens, for example, by the fact that the data in the data storage at time (tA< n -i)) the administration of the last dosage form of the medicinal product (DFAM( n-i>) present value for the therapeutically effective minimum concentration (cAMeff / MiN(tA) <n-i))) erhöht wird bzw. hierfür ein höherer Wert gespeichert wird, sofern der Zeitpunkt des Auftretens der Patientendaten betreffend eine unzureichende Arzneimittelwirkung (tuAMw) ein Zeitpunkt ist, für den die auf Basis der im Datenspeicher gespeicherten pharmakologischen, pharmakodynamischen, pharmakometrischen, pharmakogenetischen und / oder pharmakokinetischen Daten durchgeführte Berechnung der Konzentration des Arzneimittels (cAM e ff(tuAMw) in the compartment, especially in the effects compartment, is greater than the value in the data storage at time (tA< n -i)) the administration of the last dosage form (D< n -1)) of the drug (D) present value for the therapeutic minimum concentration (cAMetr / MiN(tA(ni))), such that at time (tA n) the administration of the next dosage form of the drug (DFAMn) in the data store a value for the therapeutically effective minimum concentration (cAM) e ff / MiN(tA n )) is present, which is greater than the value for the minimum concentration (cAMeff / MiN(tA) <n-i))) bei Verabreichung der letzten Dosierungsform (DFAM(n--i)). Mit anderen Worten, wenn der Patient an sich eine unzureichende Medikamentenwirkung bemerkt oder am Patienten, zum Beispiel durch einen behandelnden Arzt oder einen Pfleger oder auch durch eine automatische Messung von relevanten physiologischen Parametern, eine unzureichende Medikamentenwirkung beobachtet wird, und zwar zu einem Zeitpunkt, an dem auf der Basis der zeitabhängigen Konzentrationsberechnung umHatchmore Labs GmbH

[0574] If a sufficient drug effect was expected in the effect compartment, then it may be advantageous to increase the stored value for the minimum therapeutic concentration.

[0575] Symptoms of poor drug tolerance that are actually caused by the drug, and especially by the specific medication, often manifest at a time when the drug concentration, particularly in the effect compartment, is high. For example, at such a time, the maximum therapeutically effective concentration of the drug in the effect compartment for the individual patient may be exceeded.

[0576] In one embodiment, the electronic control device is therefore programmed such that patient data concerning insufficient drug tolerance (UMV) is taken into account when determining the time (tA). n ) and / or the dose (D n) the next dosage form of the drug to be administered to a patient (DFAMn) are taken into account by reducing a therapeutic maximum (cAMeff / MAx) stored in the data memory or by storing a lower value for it, so that at the time of administration of the next dosage form (tAn) of the drug (DFAMn) a value for the therapeutic maximum concentration (cAM) is stored in the data memory. e ff / MAx(tA n )) is present, which is smaller than the therapeutically effective maximum concentration (cAMefr / MAx(tA(ni))) for the administration of the last

[0577] Dosage form (DFAM< n -i)).

[0578] In order to achieve a balance between the desired treatment success and sometimes unavoidable mild side effects, the electronic control device can be programmed so that patient data concerning adverse drug reactions (ADR) are only taken into account by the control device if the adverse drug reaction reaches or is at least a severity level of 2, whereby the CTCAE scale as used by the American National Institutes of Health (NIH) is relevant for assessing the severity of adverse drug reactions.As already mentioned, particular attention should be paid to symptoms of insufficient drug tolerance that occur when the drug concentration, especially in the effect compartment, is high, because it is particularly likely that a symptom did not occur by chance but is related to an effect of the drug. In one embodiment, therefore, patient data concerning insufficient drug tolerance (IDT) are taken into account by the control device when the time of onset of insufficient drug tolerance (IDT) coincides with a time when the drug concentration in the effect compartment (ACC) is high. eff(tuMv)) is at least 50%, preferably at least 60%, such as at least 70%, 75%, or 80%, of the value for the therapeutically effective maximum concentration stored in the data memory at that time. In other words, the preferably calculated value for the drug concentration at the time of the occurrence of a symptom of insufficient drug tolerance, i.e., at time (tuMv), is then at least 0.5 * cAMeff / MAx, preferably at least 0.6 * cAMeff / MAx, such as at least 0.7, 0.75, or 0.8 * cAMeff / MAX.

[0579] In such a case, the electronic control device can be programmed to take into account patient data concerning insufficient drug tolerance (IDT) if the drug intolerance reaches or is at least a severity level of 1.

[0580] The term "severity of drug intolerance" or "intensity of adverse events," as used herein, refers to the "Common Terminology Criteria for Adverse Events (CTCAE)," as used by the American National Institutes of Health (NIH), National Cancer Institute, Division of Cancer Treatment & Diagnosis (DCTD) within the Cancer Therapy Evaluation Program (CTEP), for classifying adverse events in clinical trials. The CTCAE scale categorizes drug intolerances, for example, into five severity levels: mild, moderate, severe, life-threatening, and fatal. Hatchmore Labs GmbH

[0581] Adverse (drug) events are usually measured using various types of classification methods and scales, including but not limited to:

[0582] - Severity-based classification / scales: These scales categorize adverse events based on their intensity and impact on the patient's health. They typically use numerical grades to represent increasing severity, from mild to life-threatening or fatal. Some examples include the Common Terminology Criteria for Adverse Events (CTCAE), the World Health Organization (WHO) Toxicity Scale, and Hartwig's Severity Assessment Scale.

[0583] Causality Assessment Grading Scales: These scales assess the likelihood that a particular drug caused an observed adverse event. They use various criteria, such as timing, dose-response (DR) relationship, and alternative explanations, to determine the probability of causality. Examples include the Naranjo Algorithm, the WHO-UMC Causality Assessment System, and the Karch and Lasagna Scale.

[0584] Patient-Reported Outcomes (PRO) Scales: These scales focus on the patient's subjective experience of adverse events and allow patients to directly report symptoms and their impact on their quality of life. They often use numerical rating scales or questionnaires to capture the patient's perspective. Examples include the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) and the Rotterdam Symptom Checklist.

[0585] An example of a therapeutic situation in which the system according to the invention is advantageous is the titration of a drug, as may occur, for example, at the beginning of treatment, for instance with a drug for which individual differences, particularly with regard to the pharmacokinetics and / or pharmacodynamics of the drug, have been observed within the patient population in population studies, such as registration studies. In such cases, in particular, determining a suitable dose for the patient is often achieved by slowly increasing the administered dose.

[0586] In one embodiment, particularly when the dosage forms of the drug (DFAM) are available as dosage forms with different dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3), especially as dosage forms with different discrete dose options, the control device is therefore programmed such that at the first administration time (tAo) of a dosage form of the drug (AMo), it does not yet select the dose option with the highest dose (DoPTioN-max) (this could, for example, be the dose option with the lowest dose at the very beginning of treatment, so that the dosage can be increased during the course of treatment), and that it is further programmed such that at a subsequent administration time (tA n ) a dose option is selected from the various, in particular from the various discrete, dose options with a higher dose than the dose option of the time of administration (tAo) (Dn > Do). If, for example, it is then intended to select a dose option with an even higher dose at a further subsequent administration time (tA(n+i>) (D< n +1) > D n ), and then symptoms of insufficient drug tolerance (IDT) after the time of administration (tA) n ) occur, the control device is programmed to take these into account when determining the dose of the subsequent dosage form of the

[0587] Drug (DFAM)<n+i;) dahingehend zu berücksichtigen, dass die Dosis D(n+i> ) at the subsequent administration time (tA< n +i)) is not increased compared to the time of administration (tAn).

[0588] To achieve a balance between the desired treatment success and sometimes unavoidable mild side effects, the electronic control device can be programmed so that patient data concerning insufficient drug tolerance (IDG) is only considered by the control device if the insufficient drug tolerance reaches or is at least a severity level of 2, for Hatchmore Labs GmbH

[0589] The assessment of the severity of adverse drug reactions is based on the CTCAE scale, as used by the NIH DCTD. As mentioned previously, particular attention should be paid to symptoms of adverse drug reactions that occur when the drug concentration, especially in the effect compartment, is high, because in such cases, it is likely that a symptom did not occur randomly but is related to an effect of the drug.

[0590] In one embodiment, patient data concerning insufficient drug tolerance (UMV) are therefore taken into account by the control device if the time of occurrence of insufficient drug tolerance (tuMv) is a time at which the concentration of the drug in the effect compartment (cAM) eff(tuMv)) is at least 50%, preferably at least 60%, such as at least 70%, 75%, or 80%, of the value for the therapeutically effective maximum concentration stored in the data memory at that time. In other words, the preferably calculated value for the drug concentration at the time of the occurrence of a symptom of insufficient drug tolerance, i.e., at time (tuMv), is then at least 0.5 * cAMeff / MAx, preferably at least 0.6 * cAMetf / MAx, such as at least 0.7, 0.75, or 0.8 * cAMeff / MAX.

[0591] In such a case, the electronic control device can be programmed to take into account patient data concerning insufficient drug tolerance (IDT) if the drug intolerance reaches or is at least a severity level of 1.

[0592] When titrating a drug, the patient may only experience symptoms of insufficient drug tolerance at the beginning of treatment, but after some time become accustomed to higher concentrations of the drug. Therefore, if an increase in dosage is desired, it can be done gradually. In one embodiment, the control device is programmed to automatically increase the dosage at a later administration time (tA< n +y)) again a dose option with a higher dose than that of the following dose option (D< n +i)) to select (D<n+y) > D(n+1>), provided that over a period of at least three consecutive administration times (tA( n +i), tA< n +2) and tA(n+3>), which followed a time point of occurrence of a drug intolerance (tuMv), no further drug intolerance was recorded.

[0593] On the other hand, the first, initial or starting dose for a patient may already trigger an insufficient drug intolerance, as can be the case with certain cancer drugs, in which case a longer "pause" interval is chosen until the next treatment, and / or the initial dose is reduced or down-titrated.

[0594] However, if a patient repeatedly reacts negatively to a particular dose option, such a dose option should no longer be used, so in one embodiment the control device is programmed to select a dose option (D n ) no longer selectable if at least three consecutive administration times (tA) n , tA< n +i) and tA< n+ 2)) where the dose option (D n ) was administered, and at least one adverse drug reaction occurred in each case.

[0595] During the course of treatment, e.g. with a constant dose of a drug, it is possible that the patient develops a drug intolerance and now reacts negatively to concentrations of the drug that were previously tolerable for him.

[0596] In some embodiments, the electronic control device is therefore programmed to store patient data concerning the occurrence of insufficient drug tolerance (IDG) after a last administration time (tA< n -i)) to take into account that the dose of the subsequent dosage form of the medicinal product (DFAMn) at the next administration time (tA) n ) compared to the time of administration (tA< n-i)) is reduced. This means a change in the stored value for the dose, because the electronic control device was programmed at time tAo not to select the lowest dose option (DoPTioN-min) under dosage forms of the drug (DFAMo) and Hatchmore Labs GmbH

[0597] at a subsequent administration time (tA n ) to select the same dose option (D n = DOPTION-I). The dosage forms of the drug (DFAM) can be in the form of dosage forms with different dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3 < DoPTioN-max), in particular as dosage forms with different discrete dose options.

[0598] In order to achieve a balance between the desired treatment success and sometimes unavoidable minor side effects, the electronic control device can be programmed so that patient data concerning adverse drug reactions (ADR) are only taken into account by the control device if the adverse drug reaction reaches or is at least a severity level of 2, whereby the CTCAE scale as used by the American National Institutes of Health (NIH) is relevant for assessing the severity of adverse drug reactions.As already explained regarding the consideration of insufficient drug tolerance during up-titration of a drug, it is also advisable to consider insufficient drug tolerance during treatment with a constant dose of the drug, particularly when the calculated concentration of the drug in the effect compartment is close to its maximum, and then, if necessary, to consider insufficient drug tolerance (IDC) even from a severity level of 1. Similarly, analogous to the control logic described above for up-titration, the control device can be programmed to select a dose option with a higher dose at a later administration time, or to select a dose option (D. n ) should no longer be selected in cases of observed repeated intolerances.

[0599] One advantage of the system according to the invention is that the method of drug administration can be adapted to individual needs and, in particular, to the individual patient's response to the drug. For example, an individual patient may respond better to a drug than would be expected based on the experience gained from the registration studies. Or, an individual patient may respond better to a drug during the course of treatment, meaning that concentrations of the drug that were not expected to produce a sufficient effect are achieved. This can manifest as an unexpectedly faster onset of action and / or an unexpectedly prolonged effect.

[0600] In one embodiment, the invention therefore relates to a system in which the electronic control device is programmed to use patient data concerning a satisfactory drug effect (ZAMW) when determining the time (tA). n ) and / or the dose (D n ) to take into account the next dosage form (DFAMn) of the drug to be administered to a patient if the time of its occurrence (tzAMw) is a time that lies after the time of administration of the last dosage form of the drug (tA(ni>) but before the time of the last maximum (tA(ni)max) of the drug concentration cAMefr(tA(ni>max), and for which the calculation of the drug concentration in an effect compartment (cAM) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store eff(tzAMw)) is smaller than the value of a predefined minimum effective concentration in the compartment, particularly in the effect compartment (cAMetr / MiN). In particular, the value stored in the data record at the time of administration of the last dosage form of the drug (tA< n -i)) the existing value for the minimum concentration (cAMefr / MiN(tA(ni))) is reduced or overwritten accordingly if the time of onset of a satisfactory drug effect (tzAMw) is a time for which the calculation of the drug concentration in the compartment, in particular in the effect compartment, (cAM) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store, is not applicable. e ff(tzAMw)) is smaller than the value stored in the data store at the time of administration of the last dosage form of the drug (tA< n-i)) present value for the minimum concentration (cAMeff / MiN(tA(ni))), so that at the time of administration of the next dosage form of the drug (tAn) a value for the minimum concentration (cAM) is stored in the data memory e ff / MiN(tA n )) is present, which is smaller than cAMetr / MiN(tA(ni)).Hatchmore Labs GmbH

[0601] The new value is then preferably a value for the minimum concentration (cAM). e ff / MiN(tA n )), which corresponds to the calculated value of the drug concentration in the compartment, in particular in the effect compartment, (cAMefr(tzAMw)) at the time of satisfactory drug effect (tzAMw).

[0602] In a further embodiment, the invention therefore relates to a system in which the electronic control device is programmed to use patient data concerning a satisfactory drug effect (ZAMW) when determining the time (tA). n) and / or the dose (D n ) to take into account the next dosage form (DFAMn) of the drug to be administered to a patient if the time of onset (tzAMw) of satisfactory drug effect (ZAMW) is a time that lies after the time of administration of the last dosage form of the drug (tA(ni>) and after the time of the last maximum concentration of the drug (cAMeff(tA(ni)max)), and for which the calculation of the drug concentration in the effect compartment (cAMeff(tzAMw)) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store is less than the value of a predefined minimum effective concentration in the compartment, in particular in the effect compartment (cAMeff / MiN).

[0603] In particular, the data stored at the time of administration of the last dosage form of the drug (tA< n -i)) The existing value for the minimum concentration (cAMefr / MiN(tA(ni))) may be reduced or overwritten or replaced by a lower value if the time of onset of a satisfactory drug effect (tzAMw) is a time for which the drug concentration in the compartment, in particular the effect compartment (cAMeff(tzAMw)), calculated on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store, is lower than the concentration in the data store at the time of administration of the last dosage form of the drug (tA< n -i)) present value for the minimum concentration (cAMeff / MiN(tA(ni))), so that at the time of administration of the next dosage form of the drug (tA n) in the data storage a value for the minimum concentration (cAM) e ff / MiN(tA n )) is present, which is smaller than cAMetr / MiN(tA(ni)).

[0604] The new value is then preferably a value for the minimum concentration (cAM). e ff / MiN(tA n )), which corresponds to the calculated value of the drug concentration in the compartment, in particular in the effect compartment, (cAMefr(tzAMw)) at the time of satisfactory drug effect (tzAMw).

[0605] The system according to the invention makes it possible to adapt the treatment of a patient according to the effect of the drug, in particular the effect of the drug on the individual patient.

[0606] In one embodiment, a mathematical relationship between the drug effect and the dose is stored in the data storage and / or a mathematical relationship between the drug side effects and the dose is stored.

[0607] In particular, the system can then derive or use a value for the clinical benefit of a drug dose from the mathematical relationship between drug effect and dose and the mathematical relationship between drug side effects and dose, e.g., to determine the time (tAn) and / or dose (D). n ) the next dosage form of the drug to be administered to a patient (DFAMn). See also Figure 14.

[0608] For example, a dose-dependent function can be determined or used to assess the clinical benefit of a dose.

[0609] Based on such a dose-dependent function, a dose can then be selected, for example, by choosing a dose that is close to the maximum of the dose-dependent function according to clinical benefit. A dose is, for example, close to the maximum of Hatchmore Labs GmbH.

[0610] dose-dependent function, if the slope of the dose-dependent function for the clinical at the dose has a value of at most 0.5, preferably at most 0.4, particularly preferably at most 0.3, such as at most 0.2 or at most 0.1.

[0611] The electronic control device can be programmed to select between different dose options based on the dose-dependent function for clinical benefit, for example by selecting the dose option (Dx) for which the value of the dose-dependent function for clinical benefit is highest.

[0612] A mathematical relationship between drug effect and drug dose refers here to any type of dose-response (DR), exposure-response (ER), and / or dose-exposure-response (DER) relationship. Examples include a dose-response relationship (DR) that indicates at which administered dose of the drug a desired therapeutic effect occurred in a certain proportion of a population, or a dose-response relationship (DR) that indicates at which administered dose of the drug a desired therapeutic effect will occur in an individual with a certain probability. Further examples include exposure-response relationships (ER), in which the concentration of a drug or an active metabolite of the drug in a compartment is related to the probability of a desired therapeutic effect occurring.

[0613] The term "dose-value clinical benefit" is used herein to refer to any type of dose-clinical benefit relationship. Examples include a dose-clinical benefit relationship that indicates at what administered dose of the drug a desired effect occurred in a certain proportion of a population, while an undesired effect was avoided, or a dose-clinical benefit relationship that indicates at what administered dose of the drug a desired effect will occur in an individual with a certain probability, while an undesired effect will be avoided.To obtain a value for the clinical benefit of a drug dose, concentration-dependent "dose-benefit relationships" can be combined with "dose-side effect relationships" to obtain a dose-dependent function for the clinical benefit of a drug dose. This function can then be used to determine at which dose of the drug (or at which concentration of the drug in an effect compartment) there is the highest probability, for example, in an individual, that a desired effect of the drug will occur while an undesired effect will be avoided.

[0614] Towards the end of a treatment, for example with a constant dose of a medication, a patient may develop a dependence on the drug and experience drug intolerance in response to a decrease in concentration. Therefore, a gradual dose reduction is necessary to achieve a satisfactory end to treatment. For example, tapering off the medication after such a pre-treatment period is often necessary at the end of opioid treatment.

[0615] In one embodiment, the electronic control device is therefore programmed to store patient data concerning insufficient drug tolerance (IDC) that occurred after the last treatment time (tA< n-i)) occur, when determining the dose of the subsequent dosage form of the medicinal product, in such a way that the dose at the next administration time (tA) n ) compared to the time of administration (tA< n -i)) is not reduced. This is relevant in situations where the dosage forms of the medicinal product (DFAM) are available as dosage forms with different dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3), particularly as dosage forms with different discrete dose options, and where it was intended to administer a dosage form of the medicinal product (DFAMn) at the next administration time (tAn) that corresponds to a pretreatment period or preceding period with a last administration time (tA). <n-i>) follows, where the lowest dose option (DoPTioN-min) was not selected, a lower dose option will be selected at the next administration time (tAn) (D n < D n -1).Hatchmore Labs GmbH

[0616] In order to achieve a balance between the desired end of treatment and the sometimes unavoidable mild side effects, the electronic control device can be programmed so that patient data concerning insufficient drug tolerance (IDT) is only taken into account if the drug intolerance reaches a severity level of at least 2.

[0617] As already mentioned, particular attention should be paid to symptoms of insufficient drug tolerability, which occur when the drug concentration, especially in the effect compartment, is low during such a tapering process, because in such cases one can suspect that a symptom did not simply occur by chance, but is related to a certain dependence of the patient on the drug.

[0618] In one embodiment, patient data concerning insufficient drug tolerance (UMV) are therefore taken into account by the control device if the time of occurrence of insufficient drug tolerance (tuMv) is a time at which the concentration of the drug in a compartment, in particular in the effect compartment (cAM), is e ff(tuMv)) at most 50%, preferably at most 40%, such as at most 30% of the concentration of the last maximum of the concentration of the drug (cAMeff(tA(ni)max).

[0619] In one embodiment, patient data concerning insufficient drug tolerance (IDC) is also taken into account if the drug intolerance reaches at least a severity level of 1. In the long term, when tapering off a drug, the goal is naturally to further reduce the dose, even if a further dose reduction had to be postponed initially due to problems experienced by the patient.

[0620] In a further embodiment, the electronic control device is programmed such that at an administration time (tA) that lies after the next time (tAn) for the administration of the next-but-one dosage form (Dn+2)<n+2+x> ) again a dose option with a lower dose than that of the next dosage form (D n ) is selected (D< n +2+x) < D n ), if over a period of at least three consecutive administration times (tA) n , tA< n +i) and tA(n+2>), which followed a time point of occurrence of a drug intolerance (tuMv), no further drug intolerance was recorded.

[0621] During treatment, a patient, doctor, or nurse may notice that a dosage form of the medication was not taken at the intended time. This can cause the drug concentration in the effect compartment to fall below the optimal concentration for the treatment. This can be addressed, taking into account the characteristics of the drug, such as a therapeutically acceptable maximum concentration, by increasing the dose once at the next administration of that dosage form.

[0622] In one embodiment, the control device is therefore programmed to detect a missing drug intake at the last intended administration time (tA< ) taking into account patient data. n -i)) when determining the dose (D n ) the next dosage form of the medicinal product (DFAMn) to be taken into account in such a way that the dose at the next administration time (tAn) is in comparison to the administration time (tA< n -i)) is increased. This applies in particular if the dosage forms of the medicinal product (DFAM) are available as dosage forms with different dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3), such as dosage forms with different discrete dose options, and if the electronic control device at time (tA< n -i)) was programmed to select a dose option with the same dose at this next administration time (tAn) (D n = D(n-1>). Depending on the type of drug, there may be some flexibility regarding the timing of medication intake. This can be the case, for example, if the drug is administered in a dosage form that has a long time-to-peak concentration, such as at least 12 or at least 24 hours, and / or if the half-life of the drug in a compartment of the body, such as Hatchmore Labs GmbH, is long.

[0623] The half-life of the drug in the blood, and especially the plasma half-life, is very long, such as at least 12 or at least 24 hours, and / or the clearance of the drug is very low, such as at most 50 ml / min or at most 10 ml / min. In such situations, the time-dependent concentration fluctuations of the drug are often not particularly pronounced, and the patient can, for example, be given the choice of taking a higher-dose formulation of the drug per unit of time or, alternatively, two or more lower-dose formulations in the same unit of time.

[0624] In some embodiments, the control unit is therefore programmed, via the output device, to give patients a choice of dosage forms of the drug (DFAM) to take at one or more administration times per unit of time, particularly per day, according to any one of claims 40 to 95. The choice can be offered via a selection list, display of various options, e.g., on a screen, etc.

[0625] In particular, the dispensing device can suggest or recommend an increase or decrease in the number of administration times to the patient. For example, at a final administration time (tA< n -i)) A value for a specific number of administrations of the drug dosage form is stored in the system, such as the usual dosage regimen of an approved drug from the package insert. If the control unit now detects that the patient requires a higher frequency of administrations or can manage with a lower frequency of doses based on their individual pharmacokinetic and / or pharmacodynamic parameters, the system suggests a higher frequency to the patient starting at the next administration time (tA). n ) in an embodiment according to the invention, an increase or reduction in the number of administration times per unit of time is provided.

[0626] In some embodiments, the system may be provided by means of which the dispensing device indicates the time at which the minimum concentration (cAMeff / MiN) is reached and / or falls below, and / or prompts the patient to administer or take the drug (D) before reaching the time at which the minimum concentration (cAMetr / MiN) is reached and / or falls below.

[0627] The system and its control were explained using a drug as an example. Experts know that there are drugs that are not active themselves, but are metabolized in the body into the actually active substance, the "active metabolite" or active metabolites.

[0628] In such a case, the person skilled in the art will understand that the control will be achieved by determining or calculating the respective concentration of the active metabolite and will replace a reference to the drug (D) with a reference to the active metabolite of the drug (AMB) so that the meaning of the respective statement remains correct. In situations where the drug AND at least one active metabolite of the drug are responsible for the effect, they will replace a reference to the drug with a correct reference to the drug AND the active metabolite of the drug (which, for example, can be understood as meaningless).

[0629] In such situations, he can also perform more complex calculations, taking into account the respective effectiveness of the drug and active metabolite(s), and weighting the drug and active metabolite accordingly.

[0630] If, for example, the drug and its active metabolite contribute differently to the drug's effect—for instance, because both bind to the same pharmacological target but with different affinities—then their "weighted sum" can be considered, particularly in pharmacodynamic calculations. Thus, if, for example, an active metabolite of the drug binds nine times more strongly to the pharmacological target and inhibits it nine times more strongly than the unmetabolized drug itself, the weighted sum of the drug and its metabolite can be calculated by multiplying the concentration of the drug's active metabolite by nine times the concentration of the drug's active metabolite by nine times the concentration of the drug's active metabolite. (Hatchmore Labs GmbH)

[0631] The weighted sum is weighted more heavily than the concentration of the drug itself. In practice, in complex situations where both the drug itself and its active metabolite(s) contribute to the drug's effect to varying degrees, a new pharmacokinetic model and / or dose-response model and / or dose-exposure-response model is often developed that takes into account the different efficacy and / or pharmacokinetics of the pharmaceutically active drugs and / or metabolites. In one embodiment of the invention, the "weighted sum" refers to such a complex model.

[0632] In situations where an active metabolite is responsible for side effects, for example, he will be able to make such a weighting based on the severity of the respective side effects of the drug and the active metabolite.

[0633] A “meaningful reference to an active metabolite of the drug” can mean that whenever the term “drug” is used herein, for example in the examples, it also refers to an “active metabolite of the drug,” but the word “drug” is not simply replaced one-to-one, but is replaced in such a way that the core of the statement made for the “drug” in connection with the active metabolite of the drug is preserved and makes scientific sense.

[0634] One advantage of the system is that the continuous collection of patient data during treatment can yield new insights into the patient. In particular, individual physiological characteristics of the patient can be identified if, for example, their response to the administration of a particular dosage form of the drug differs from what would be expected for an average patient, both in terms of drug effect and / or side effect(s).While, as a rule, at the beginning of treatment the data storage contains values ​​for pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic parameters that were taken from the scientific literature or obtained on the basis of the data collected in the context of the approval studies, the system according to the invention makes it possible to recognize deviations of the patient from such an assumed “norm” and to individualize one or more of these parameters.

[0635] In one embodiment, the invention therefore relates to a system in which the control device is programmed to change the value for the bioavailability of a drug (D) in the given dosage form (DFAM) present in the data storage at the beginning of a patient's treatment for the further treatment of the same patient if the observed pharmacokinetics of the drug (D) in this patient suggest that the value for the bioavailability of the drug (D) present in the data storage at the beginning of the patient's treatment does not correctly, or not as expected, describe the individual bioavailability of the drug (D) in the patient.If, for example, a much higher amount of the drug integrated over time (area under the curve) is observed in the blood plasma during pharmacokinetic monitoring than would be expected based on pharmacokinetic experience, this may indicate an individual characteristic of the treated patient that is taken into account according to the invention. Likewise, deviations in individual pharmacokinetic parameters can be detected by observing the pharmacokinetics of the administered drug and then taken into account according to the invention.

[0636] Accordingly, in some embodiments, the invention relates to a system in which the initial values ​​for the volume of distribution of the drug (D), and / or for the time-to-peak concentration (tmax (D)) of the drug (D), and / or for the half-life of the drug in a compartment of the body, such as the half-life of the drug in the blood and in particular the blood plasma half-life, and / or for the clearance of the drug, are changed for the further treatment of the same patient if the observed pharmacokinetics of the drug in this patient suggest that the value present in the data storage at the beginning of a patient's treatment will correspond to the Hatchmore Labs GmbH

[0637] The individual value for this parameter in the patient's body is not accurately described, or not as expected.

[0638] With the ability to individualize PK and PD parameters during treatment, the system according to the invention, in one embodiment, offers the flexibility to capture interindividual variability and take it into account in further treatment. Interindividual variability of PK parameters can have many different causes, for example:

[0639] - Age

[0640] Gender

[0641] body weight

[0642] Body Mass Index (BMI)

[0643] Body composition (e.g., body fat percentage, muscle mass)

[0644] Genetic material (e.g., pharmacogenomics / pharmacogenetics)

[0645] Kidney function

[0646] Liver function

[0647] Gastrointestinal function

[0648] Cardiac output

[0649] Blood flow to the organs

[0650] Plasma protein levels (e.g., albumin, alpha-1-acid glycoprotein)

[0651] metabolism

[0652] Hormonal status

[0653] Smoking status

[0654] Pregnancy status

[0655] Circadian rhythms

[0656] Medical condition (e.g., critical illness, sepsis, organ failure) Comorbidities

[0657] alcohol consumption

[0658] Nutrition and interactions between foods

[0659] Physical activity

[0660] Allergies

[0661] Phenotype

[0662] Environmental factors (e.g. altitude, temperature)

[0663] Concomitant medication (drug interactions)

[0664] Current and / or past drug use / exposure

[0665] Stress level

[0666] Inflammation status

[0667] acid-base balance

[0668] Electrolyte content

[0669] pH level of the stomach

[0670] Transit time in the intestine

[0671] Permeability of the blood-brain barrier

[0672] vascular permeability

[0673] Skin permeability (for topical medications)

[0674] Lung function (with inhaled medications)

[0675] Blood flow to the tissue

[0676] Oxygen saturation

[0677] Viscosity of blood

[0678] Bile flow and composition

[0679] Function of the lymphatic system

[0680] Immune system status

[0681] Presence of drug-metabolizing enzyme inducers or inhibitors; expression and function of transporter proteins

[0682] Receptor polymorphisms

[0683] microbiome

[0684] The above list includes further patient data as it may be used here in the context of the feedback device and / or data acquisition device. Hatchmore Labs GmbH

[0685] Similarly, interindividual variability in PD parameters can have many different causes, such as differences in the level and / or spatial distribution of gene expression of the drug's pharmacological target, differences in the binding behavior of the drug and its pharmacological target, and differences in the sensitivity and kinetics of signal transduction cascades downstream of the drug's pharmacological target, to name just a few. Such differences result in each individual patient having a unique dose-response (DR) curve and / or dose-exposure-response (DER) curve—that is, an individual mapping of a drug concentration in a compartment, particularly the effect compartment, to an expected value for the onset of a desired drug effect at that concentration.In one embodiment, dose-response (DR) curves and / or dose-exposure-response (DER) curves can therefore be individualized in the system.

[0686] With this approach, it is no longer necessary to "estimate" acceptable "safe" doses based on weak, small-scale dose-finding trials. Instead, one waits for sufficient data (N) across a very broad dose range to truly understand the full picture. This is not only the right thing for patients, but it also allows both the pharmaceutical company and regulatory authorities to determine the most appropriate dose range for approval, which may or may not correspond to the actual doses used in the supporting studies.

[0687] The invention described here is a (modular) personalized dosing system for determining an optimized dosing regimen for each individual patient. This is achieved, for example, by controlling the determination of the dose or the administration times through measurements of efficacy, safety, and tolerability (or any combination thereof) during treatment. This has, among other advantages:

[0688] 1. that the system can determine an individually optimized dosage regimen based on the individual characteristics of the patient; and / or

[0689] 2. that the system can determine whether the original dosage regimen needs to be changed for reasons of efficacy and / or safety and / or tolerability, and how this can best be accomplished; and / or

[0690] 3. that the system can help determine the circumstances for discontinuing the dosing regimen, e.g., when no dose is found for the patient that has a sufficiently positive benefit-risk ratio to justify further administration.

[0691] In clinical practice, determining an individually optimized dosage regimen means finding the individual optimum between efficacy, safety and tolerability in treatment with a drug.

[0692] Personalized drug dosing requires an understanding of the dose-response (DR) relationship at the individual patient level, rather than at the patient population level. Fundamentally, when discussing the DR relationship, a crucial distinction must be made between the population-wide DR relationship and individual DR relationships. It is essential to understand that individuals have their own unique DR relationships (the aforementioned interindividual variability in DR) for efficacy, tolerability, and safety responses.

[0693] Based on this individual DR relationship, it is possible to construct a so-called Clinical Utility Index (CUI), which balances the benefit of efficacy with increasing dose against the "harms" in terms of tolerability and / or safety with increasing dose. Hatchmore Labs GmbH

[0694] A simple CUI can, for example, define a "benefit" score that equates to effectiveness vs.

[0695] The weighting is 1:1:3 for tolerability versus triple safety (i.e., the relative weighting is 1:1:3 for these three endpoints). In this example, patients, together with their healthcare provider, can continuously evaluate each attribute to better understand and manage the benefit (benefit / risk) of drug therapy.

[0696] The population DR curve summarizes the average individual responses to each dose. Because individual DR relationships to dose are non-linear, the population DR relationship cannot even be considered a dose-response relationship for a "typical" person, as individuals exhibit highly variable individual DR relationships compared to the population DR. Therefore, increasing the dose at the individual level will not move patients along the population DR curve, but rather along their individual DR curve. The key lies in understanding these individual DR relationships, as they determine (i) the optimal dose for each individual patient and (ii) the optimal dose titration algorithm.

[0697] Returning to the simple CUI example, a relative weighting of 1:1:3 might yield a maximum benefit for the patient population average at, say, 10 mg, while individual "optimal" doses could range from, for example, 4 mg to over 40 mg, a range more than tenfold for individual patients. Therefore, it is reasonable to conclude that a population DR relationship says nothing about the underlying DR relationships for individual patients.

[0698] Furthermore, in clinical drug trials where each individual patient contributes data only from a single fixed dose regimen (or exposure level), the data generated across individuals and doses can only determine the population-wide DR (Drug Reduction) ratio. This is frequently the case in Phase Z dose-finding trials using a parallel-group design. Here, different cohorts of individuals receive different doses (e.g., placebo and 5 mg, 10 mg, 20 mg, 40 mg, and 80 mg), but intra-individual dose titration is lacking. The resulting DR relationships are therefore population-wide DR relationships, and any decision regarding the (optimal) "one-size-fits-all" dose completely ignores the underlying individual DR relationships.

[0699] This means that different individual DR relationships (i) can result in the same population DR relationships, and (ii) knowledge of the population DR does not provide the necessary information to determine the correct dose for each individual patient. In this example, as in real life, attempting to administer the same dose to everyone will result in some people being underdosed and some people being overdosed. Furthermore, knowledge of the population DR provides no information to help patients who wish to adjust their dose to manage adverse events.

[0700] Current (clinical) development, trial, and personalized medicine approaches cannot answer the question: "If the patient reduces their dose due to severe adverse events, how will this affect their future outcomes?" It is possible that patients who reduce their dose will show better results than those who do not, because the first group may have higher average drug concentrations and be more sensitive to the medication. Therefore, one cannot simply say a priori that every downward dose reduction in a (non-randomly selected) group of patients will lead to worse average outcomes compared to patients taking the original dose. The available population-based dose reduction (DR) is not meaningful here, as it says nothing about individual patients.

[0701] Quantifying individual DER relationships requires measuring the effect for multiple dose and / or exposure levels from a flexible dosing regimen. Combined with appropriate designs and analyses, this enables the quantification of interindividual variability in DER. Hatchmore Labs GmbH

[0702] The system according to the invention achieves this by providing interacting system components that capture and process patient feedback and take it into account when determining the individually optimized dosage regimen. Hatchmore Labs GmbH

[0703] The invention further relates to the following embodiments according to the invention:

[0704] 1. System (100) for determining the time and / or dose of a drug (D) to be administered to a patient (P), the system (100) comprising, or consisting of, the following functional components,

[0705] an electronic control device (9);

[0706] a data storage device (M) for storing at least

[0707] of administration times (tAo, tAi, tA2,..., tA(ni>) of one or more previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)) and / or the dose (Do, Di, D2,..., D(ni>) of these previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni));

[0708] a feedback device (8) for recording patient data relating to the patient's response to administration of a dosage form of the medicinal product (DFAM);

[0709] wherein the electronic control device (9) is further programmed to

[0710] Reading data stored in the data storage (M);

[0711] Evaluating the patient data acquired by the feedback device (8); and to

[0712] Determining the time (tA) n , tA< n +i), tA< n +2),..., tA(n+x>) and / or the dose (D n , D(n+i;, D(n+2>,..., D(n+x>) for the administration of the next or further dosage form(s) of the medicinal product (DFAMn, DFAM<n+i), DFAM(n+2> ,..., DFAM(n+x>) taking into account the read and recorded data;

[0713] an output device, in particular an information output device (17), for outputting information at the determined time(s) (tA n , tA< n +i), tA(n+2>,..., tA(n+x>) and / or the determined dose (D n , D<n+1), D(n+2),..., D(n+x> ) concerning the next or further dosage form(s) of the medicinal product (DFAM), or for dispensing the next or further dosage form(s) of the medicinal product (DFAM).

[0714] 2. System (100) according to embodiment 1, wherein the data storage (M) comprises pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data relating to the drug (D) and / or one or more active metabolites of the drug (DB).

[0715] 3. System (100) according to embodiment 2, wherein the pharmacological, pharmacodynamic, pharmacometric, pharmacokinetic and / or pharmacogenetic data relating to the drug (D) and / or one or more active metabolites of the drug (DMB) are or comprise pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the drug (D) and / or one or more of the active metabolites of the drug (DMB).

[0716] 4. System (100) according to embodiment 2 or 3, wherein the data storage (M) comprises numerical values, the numerical values ​​describing:

[0717] which proportion of the drug (D) from a given dosage form of the drug (DFAM) is absorbed by the body; and / or Hatchmore Labs GmbH

[0718] how the drug (D) is distributed in the body; and / or

[0719] how long it takes for the concentration of the drug (D) in a compartment of the body, such as the blood, and especially the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM); and / or

[0720] how long it takes for the concentration of an active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM); and / or

[0721] how quickly the concentration of the drug (D) in a compartment of the body, such as the blood, and in particular the blood plasma, decreases per unit of time; and / or how quickly the concentration of an active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma, decreases per unit of time; and / or

[0722] the amount of the drug (D) that is excreted from the body per unit of time; and / or

[0723] the amount of an active metabolite of the drug (AMB) that is excreted from the body per unit of time; and / or

[0724] which concentration of the drug (D) is assigned to a desired drug effect; and / or

[0725] which concentration of an active metabolite (AMB) of the drug (AM) is associated with a desired drug effect; and / or

[0726] which concentration of the drug (D) is attributed to an adverse drug reaction; and / or

[0727] which concentration of an active metabolite (AMB) of the drug (AM) is associated with an adverse drug reaction.

[0728] 5. System (100) according to embodiment 4,

[0729] wherein the numerical value describing the proportion of the medicinal product (MP) from a given dosage form of the medicinal product (DFMP) that is absorbed by the body is or comprises the bioavailability of the medicinal product (MP) in the given dosage form of the medicinal product (DFMP); and / or

[0730] wherein the numerical value describing how the drug (D) is distributed in the body is or indicates the volume of distribution of the drug (D); and / or wherein the numerical value describing how long it takes for the concentration of the drug (D) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM) is the time-to-peak concentration of the drug (tmax(D)); and / or

[0731] where the numerical value describing how long it takes for the concentration of an active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM) is the "time-to-peak concentration" (tmax(AMB>)) of an active metabolite of the drug (AMB); and / or Hatchmore Labs GmbH

[0732] where the numerical value describing how quickly the concentration of the drug (D) in a compartment of the body, such as the blood, and in particular the blood plasma, decreases per unit of time is the half-life of the drug (D) in a compartment of the body, such as the blood, and in particular the blood plasma half-life; and / or

[0733] where the numerical value describing how quickly the concentration of an active metabolite of the drug (AMB) decreases in a compartment of the body, such as the blood, and in particular the blood plasma, per unit of time is the half-life of the active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma half-life; and / or where the numerical value describing the amount of the drug (AM) eliminated from the body per unit of time is the clearance of the drug (AM); and / or

[0734] where the numerical value describing the amount of an active metabolite of the drug (AMB) that is eliminated from the body per unit of time is the clearance of the active metabolite of the drug (AMB); and / or

[0735] where the numerical value describing the concentration of a drug (D) associated with a desired drug effect is a therapeutically effective minimum concentration of the drug in an effect compartment (cAMeff / MiN); and / or

[0736] where the numerical value describing the concentration of the drug's active metabolite (AMB) associated with a desired drug effect is a therapeutically effective minimum concentration of the drug's active metabolite in an effect compartment (cAMBeff / MiN); and / or

[0737] where the numerical value describing the concentration of the drug (D) associated with an adverse drug reaction is a therapeutically acceptable maximum concentration of the drug in an effect compartment (cAMetr / MAx); and / or

[0738] where the numerical value describing the concentration of the drug's active metabolite (AMB) associated with an adverse drug reaction is a therapeutically acceptable maximum concentration of the active metabolite in an effect compartment (cAMBetr / MAx).

[0739] 6. System (100) according to embodiment 4 or 5, wherein the data storage (M) comprises values ​​relating to the statistical distribution for one or for several or for all of the mentioned and / or stored numerical values.

[0740] 7. System (100) according to embodiment 6, wherein the values ​​relating to the statistical distribution of the numerical values ​​relate to pharmacokinetic and / or pharmacodynamic population studies, in particular wherein the values ​​relating to the statistical distribution of the numerical values ​​represent the variance and / or standard deviation of the values ​​in question in pharmacokinetic and / or pharmacodynamic population studies.

[0741] 8. System (100) according to one of embodiments 4 to 7, comprising a writing device (13) programmed to write or overwrite one or more or all of the numerical values ​​in the data memory (M) during a treatment.

[0742] 9. System (100) according to embodiment 8, wherein the control device (9) or the writing device is programmed to individualize one or more or all of the numerical values ​​for the patient (P) during the course of treatment. Hatchmore Labs GmbH

[0743] 10. System (100) according to at least one of embodiments 8 and 9, programmed to change, such as overwrite or replace or supplement with a more up-to-date, the value stored in the data storage (M) for a therapeutically effective minimum concentration of the drug in an effect compartment (cAMeff / MiN) and / or the value for a therapeutically effective minimum concentration of an active metabolite of the drug in an effect compartment (cAMBetr / MiN) during the course of treatment.

[0744] 11. System (100) according to one of embodiments 8 to 10, programmed to change the value for a therapeutically acceptable maximum concentration of the drug in an effect compartment (cAMetf / MAx) and / or the value for a therapeutically acceptable maximum concentration of an active metabolite of the drug in an effect compartment (cAMBetf / MAx) during the course of treatment, for example by overwriting or replacing or supplementing with a more up-to-date one.

[0745] 12. System (100) according to one of the preceding embodiments,

[0746] further showing

[0747] a recording device (11) for recording a pattern of administration of the medicinal product (MP) to the patient (P), the administration pattern at least comprising

[0748] the time of administration (tA< n -i)) and the dose (D< n -1)) the most recently administered dosage form of the medicinal product (DFAM); wherein the electronic control device (9) is further programmed to evaluate or take into account the administration pattern detected by the detection device (11); and

[0749] the determination of the time and / or dose of the next or further dosage form(s) of the medicinal product (DFAM) to be administered to the patient (P) is carried out taking into account the recorded administration pattern or the evaluation.

[0750] 13. System (100) according to embodiment 12, wherein the administration pattern comprises the time(s) of administration (tA) and the dose of all administered dosage forms of the drug (DFAM).

[0751] 14. System (100) according to embodiment 12 and / or 13, wherein the detection device (11) is programmed to record data on the patient's (P) food intake.

[0752] 15. System (100) according to one of embodiments 12 to 14, wherein the detection device (11) is programmed to detect individual physiological parameters of the patient (P).

[0753] 16. System (100) according to embodiment 15, wherein the individual physiological parameters include or consist of the weight, sex, body mass index, and / or information on the genotype of the patient (P).

[0754] 17. System (100) according to one of the preceding embodiments,

[0755] further showing

[0756] a dosage form of the drug (DFAM).

[0757] 18. System (100) according to embodiment 17, further comprising

[0758] Multiple dosage forms of the drug (DFAM) with various, preferably discrete, dosage options. Hatchmore Labs GmbH

[0759] 19. System (100) according to one of the preceding embodiments,

[0760] where determining, calculating, looking up, or reading, in each case from a storage medium, the dose (D n ) the next dosage form of the drug (DFAM) to be administered to the patient (P), comprises or consists of. 20. System (100) according to any of the preceding embodiments,

[0761] where determining the time of delivery (tA) is the calculation of the delivery time. n ) the next dosage form of the medicinal product (DFAM) includes or consists of.

[0762] 21. System (100) according to one of the preceding embodiments,

[0763] wherein the output device is used as an information output device (17) to output information at the determined time (tA) n ) and / or the determined dose (Dn) of the next dosage form of the medicinal product (DFAM) relating to the information is displayed visually or audibly on a device or is configured to do so or is prepared to transmit a signal to a device for this purpose.

[0764] 22. System (100) according to embodiment 21,

[0765] where the device may be or include a monitor, a display, a computer, a laptop, a tablet, an e-reader, a personal assistant, a comprehensive device, a smartphone, a wearable, a smartwatch, smart glasses, a sensor, a speaker.

[0766] 23. System (100) according to one of the preceding embodiments,

[0767] wherein the feedback device (8) is configured to record patient data relating to the time of feedback or the time of the patient's response (P) to administration of a dosage form of the drug (DFAM).

[0768] 24. System (100) according to one of the preceding embodiments,

[0769] wherein the feedback device (8) is configured to record patient data relating to the nature of the patient's response (P) to administration of a dosage form of the drug (DFAM).

[0770] 25. System (100) according to one of the preceding embodiments,

[0771] wherein the feedback device (8) is configured to collect patient data relating to the drug effect.

[0772] 26. System (100) according to embodiment 25,

[0773] where patient data relating to the drug effect include the time (tUAMW) of an insufficient drug effect (UAMW).

[0774] 27. System (100) according to embodiment 25,

[0775] where the patient data relating to the drug effect include the time (tzAMw) of a satisfactory drug effect (ZAMW) in patients (P).

[0776] 28. System (100) according to one of the preceding embodiments,

[0777] wherein the feedback device (8) is configured to collect patient data relating to drug tolerance (DT).

[0778] 29. System (100) according to embodiment 28, Hatchmore Labs GmbH

[0779] where the patient data concerning drug tolerance include the time (tuMv) of insufficient drug tolerance (UMV).

[0780] 30. System (100) according to embodiment 28,

[0781] where the patient data concerning drug tolerance include the time (tzMv) of satisfactory drug tolerance (ZMV).

[0782] 31. System (100) according to one of the preceding embodiments,

[0783] wherein the patient data recorded by the feedback device (8) are recorded or read in by operation of the feedback device (8) by a person and / or automatically by a device.

[0784] 32. System (100) according to embodiment 31,

[0785] wherein the feedback device (8) is configured to record patient data when the patient (P) operates the feedback device (8).

[0786] 33. System (100) according to embodiment 31,

[0787] having or connected to a device (19) for (automatic) recording of patient data, wherein the device (19) records and / or reads the blood pressure, temperature, blood glucose level, heart rate, blood oxygen saturation, respiratory rate, electrical activity of an organ, drug concentration in urine and / or CO2 content of the patient's (P) breath.

[0788] 34. System (100) according to one of the preceding embodiments,

[0789] wherein the feedback device (8), or some or all functional components of the feedback device (8), on the one hand, and the output device (17) on the other hand, are part of the same device or apparatus.

[0790] 35. System (100) according to one of the preceding embodiments,

[0791] wherein the electronic control device (9), or some or all of the functional components of the electronic control device (9), on the one hand, and the data storage device (M) on the other hand, are part of the same device or apparatus.

[0792] 36. System (100) according to one of the preceding embodiments 12 to 35, each with reference to embodiment 12,

[0793] wherein the electronic control device (9), or some or all functional components of the electronic control device (9), on the one hand, and the detection device (11), on the other hand, are part of the same device or apparatus.

[0794] 37. System (100) according to one of the preceding embodiments 12 to 36, each with reference to embodiment 12,

[0795] wherein the output device (17), or some or all functional components of the output device (17), on the one hand, and the detection device (8) on the other hand, are part of the same device or apparatus.

[0796] 38. System (100) according to one of the preceding embodiments 12 to 37, each with reference to embodiment 12, Hatchmore Labs GmbH

[0797] wherein the feedback device (8), or some or all of the functional components of the feedback device (8), on the one hand, and the detection device (11) on the other hand, are part of the same device or apparatus.

[0798] 39. System (100) according to embodiment 37 or 38,

[0799] wherein the output device (17), the acquisition device (11) and the feedback device (8), and / or their functional components, are part of the same device or apparatus.

[0800] 40. System (100) according to one of the preceding embodiments,

[0801] wherein the electronic control device (9) is further programmed such that the determination of the time (tA) n ) and / or the dose (D n ) the next dosage form of the drug (DFAM) to be administered to a patient (P) is determined by relating the patient data recorded by the feedback device (8) at at least one specific time, or for that time, to a determination, in particular calculation, of the concentration of the drug (cAM) and / or the active metabolite of the drug (cAMB) in a compartment of the patient's body (P) for the same time, carried out by the electronic control device (9) on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M).

[0802] 41. System (100) according to embodiment 40,

[0803] wherein the electronic control device (9) is programmed to assume a volume of distribution in the patient's body (P) of at least 0.15 l / kg for the drug (D) and / or the active metabolite of the drug (MB).

[0804] 42. System (100) according to embodiment 41,

[0805] wherein the electronic control device (9) is programmed to assume a volume of distribution of at least 0.5 l / kg for the medicinal product (MP) and / or an active metabolite of the medicinal product (MP).

[0806] 43. System (100) according to one of the embodiments 40 to 42,

[0807] wherein the electronic control device (9) is programmed to assume a one-compartment model or a two-compartment model for the pharmacokinetics of the drug (cAM(t)) and / or the active metabolite of the drug (cAMB(t)).

[0808] 44. System (100) according to embodiment 43,

[0809] where one compartment of the body is not the central compartment, or where none of the compartments is the central compartment.

[0810] 45. System (100) according to embodiment 43,

[0811] where one compartment of the body, or at least one of the compartments, is the peripheral compartment.

[0812] 46. ​​System (100) according to one of the embodiments 40 to 45,

[0813] wherein the pharmacokinetics of the drug (cAM(t)) and / or the active metabolite of the drug (cAMB(t)) are described by a model with at least three compartments, e.g., at least one three-compartment model. Hatchmore Labs GmbH

[0814] 47. System (100) according to one of the embodiments 40 to 46,

[0815] where one compartment of the body, or at least one of the compartments, is the effect compartment.

[0816] 48. System (100) according to one of the embodiments 40 to 47,

[0817] where determining the concentration of the drug (cAM) in a compartment and / or the active metabolite of the drug (cAMB) in a compartment is an estimate based on experience.

[0818] 49. System (100) according to one of the embodiments 40 to 47,

[0819] wherein determining the concentration of the drug (cAM) in a compartment and / or the concentration of the active metabolite of the drug (cAMB) in a compartment is or comprises a calculation of the concentration of the drug in a compartment (cAMeff) and / or the concentration of the active metabolite of the drug in a compartment (cAMBetf) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M).

[0820] 50. System (100) according to embodiment 49,

[0821] wherein the calculation performed on the basis of the data stored in the data storage (M) is based on or consists of pharmacodynamic and / or pharmacokinetic data.

[0822] 51. System (100) according to one of embodiments 40 to 50,

[0823] wherein the electronic control device (9) is programmed,

[0824] to read pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data from the data storage (M), which show a time course of the drug concentration (cAM). e to map the time course of the drug concentration (cAM) in the patient's body (P) and then, based on this time course, to determine the concentration of the drug (cAM). e ff(t)) the time (tAnmax) and / or the magnitude of the next maximum concentration of the drug (cAM) e to calculate ff(tAnmax)) in the compartment; and / or to determine the time course of the concentration of the drug's active metabolite (cAMB). e to map or calculate and / or represent ff(t)) in the patient's body (P), and then, based on this time course, the concentration of the active metabolite of the drug (cAMB) e ff(t)) the time (tAnmax-AMβ) and / or the magnitude of the next maximum concentration of the active metabolite of the drug (cAMB) e to calculate ff(tAnmax-AMB)) in the compartment.

[0825] 52. System (100) according to embodiment 51,

[0826] where the body compartment is not the central compartment.

[0827] 53. System (100) according to one of embodiments 51 to 52, with reference to embodiment 26,

[0828] where patient data concerning inadequate drug response (ADR) are used in determining the time point (tA) n ) and / or the dose (D n ) the next dosage form of the drug to be administered to a patient (P) (DFAM) is not taken into account if the time of its occurrence (tuAMw) is a time that is after the time (tA< n -i)) the administration of the last dosage form of the medicinal product (DFAM< n - i;), but before the time of the last maximum concentration of the drug (cAMeff(tA(ni)max)), and if for that time the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M) are available. Hatchmore Labs GmbH

[0829] calculated concentration of the drug (cAMefr(tuAMw)) in an effect compartment is less than the value of a predefined minimum effective concentration of the drug in the compartment, in particular less than the value of a predefined minimum therapeutically effective concentration of the drug (cAMetr / MiN) in the effect compartment.

[0830] 54. System (100) according to one of the preceding embodiments 40 to 53, wherein the electronic control device (9) is programmed to determine the next dosage form (DFAMn) to be administered to the patient (P) in such a way that the next maximum of the drug in the compartment (cAMneff / MAx) is a predetermined therapeutic value stored in the data memory (M).

[0831] The maximum (cAMetf / MAx) in the compartment, especially in the effects compartment, will not be exceeded.

[0832] 55. System (100) according to one of embodiments 40 to 54, wherein the electronic control device (9) is programmed,

[0833] to read pharmacological, pharmacodynamic, pharmacogenetic, pharmacometric and / or pharmacokinetic data from the data storage (M) which depict a time course of the concentration of the drug (cAM(t)) in the body of the patient (P), and then to calculate, based on these, the concentration (cAM(tA nmax + tx )) at a time point (tA nmax + tx ) located after the next maximum (cAnmax) of the concentration in a compartment, in particular in the effect compartment.

[0834] 56. System (100) according to embodiment 55, wherein the electronic control device (9) is programmed,

[0835] to, if the dose (D n ) the next dosage form to be administered (DFAMn) is specified, when determining its time (tA) n ) of administration to the patient (P), taking into account data stored in the data storage (M) and a therapeutic minimum concentration (cAMeff / MiN) maintained in the data storage (M), the time (tA n ) such that the concentration (cAM(tA) n )) after a final maximum of the concentration (c(tA< n -i))max) does not fall below the value for the specified therapeutically effective minimum concentration (cAMeff / MiN) in the compartment, especially in the effect compartment.

[0836] 57. System (100) according to embodiment 56, wherein the electronic control device (9) is programmed,

[0837] to, provided that for the administration of the next-but-one dosage form of the medicinal product (DFAM) <n+i;) verschiedene diskrete Optionen für den Zeitpunkt der Verabreichung (wie z. B. tAoPTioN-i < tAoPTioN-2 < tAoPTioN-3), etwa im Datenspeicher (M), vorliegen,

[0838] the option (tAoPTioN) for the time (tA< n +i)) to select the next-but-one dosage form for which the time (tA( n +i>) is at the latest after the time (tAn) of the next administration, and at what time (tA( n +i>) the concentration (cAM(tA) <n+i;) eine vorgegebenen therapeutisch wirksame Minimalkonzentration (cAMetr / MiN) nicht unterschreitet.

[0839] 58. System (100) according to embodiment 55, wherein the electronic control device (9) is programmed,

[0840] to, provided that the time (tA< n +i)) the next-but-one dosage form to be administered (DFAM) <n+i;) vorgegeben ist, beim Ermitteln der Dosis (D n ) the next dosage form of the drug to be administered to the patient (P) (DFAM(n>), taking into account data stored in the data storage (M) and a therapeutically effective minimum concentration (CAMeff / MiN) held in the data storage (M),

[0841] the dose (D n ) the next dosage form of the drug (DFAM(n>) such as Hatchmore Labs GmbH

[0842] determine that the concentration of the drug (cAM(tA) <n+i))) zum Zeitpunkt (tA< n +i;) the intended administration of the next-but-one dosage form (DFAM) <n+i;) nach einem nächsten Maximum (cAMnmax) der Konzentration die vorgegebene therapeutisch wirksame Minimalkonzentration (cAMeff / MiN) nicht unterschreiten wird.

[0843] 59. System (100) according to embodiment 58, wherein the electronic control device (9) is programmed,

[0844] in order to select, if the dosage forms of the drug (DFAM) are available as dosage forms with different discrete dose options (such as DOPTION-I < DOPTION-2 < DOPTION-3), the dose option with the lowest dose (DoPTioN-min) as the next dosage form,

[0845] with which the concentration (cAM(tA< n +i)) at time (tA< n +i)) the intended administration of the next-but-one dosage form (DFAM) <n+i;) nach einem nächsten Maximum (cAMnmax) der Konzentration eine vorgegebene therapeutisch wirksame Minimalkonzentration (cAMetr / MiN) nicht unterschritten wird.

[0846] 60. System (100) according to one of the embodiments 51, 52, 56, 57, 58 and / or 59, wherein the electronic control device (9) is programmed,

[0847] that patient data concerning an inadequate drug response (ADR) in determining the time point (tA) n ) and / or the dose (D n ) the next dosage form of the drug (DFAMn) to be administered to a patient (P) must be taken into account,

[0848] provided that the time of its occurrence (tuAMw) is a time that is after the time (tA< n - i;) the administration of the last dosage form of the drug, and after the time of the last maximum (tA(ni)max) of the concentration of the drug cAM.

[0849] 61. System (100) according to embodiment 60, wherein the electronic control device (9) is programmed,

[0850] to store the data in memory (M) at time (tA< n -i)) the administration of the last dosage form of the medicinal product (DFAM( n -i>) to increase the existing value for the therapeutically effective minimum concentration (cAMeff / MiN(tA(ni))) if the time of occurrence of the patient data concerning an inadequate drug effect (tuAMw) is a time for which the calculation of the drug concentration (cAM) based on the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store (M) e ff(tuAMw) in the compartment, especially in the effects compartment, is greater than the value in the data storage (M) at time (tA< n -i)) the administration of the last dosage form (D< n -1)) of the drug (AM) present value for the therapeutic minimum concentration (cAMeff / MiN(tA(ni))), such that at time (tA n ) of the administration of the next dosage form of the drug (DFAMn) in the data store (M) a value for the therapeutically effective minimum concentration (cAMeff / MiN(tA) n )) is present, which is greater than the value for the minimum concentration (cAMeff / MiN(tA(ni))) when administering the last dosage form (DFAM< n -i)).

[0851] 62. System (100) according to one of embodiments 40 to 61, wherein patient data relating to insufficient drug tolerance (ID) are used to determine the time (tAn) and / or dose (D). n ) the next dosage form of the drug (DFAMn) to be administered to a patient (P) is taken into account by reducing a therapeutic maximum (cAMeff / MAx) stored in the data store (M) so that at the time of administration of the next dosage form (tAn) of the drug (DFAMn) a value for the therapeutic maximum concentration (cAM) is stored in the data store (M). e ff / MAx(tA n )) is present, which is smaller than the therapeutically effective maximum concentration (cAMeff / MAx(tA) <n-i))) für die Verabreichung der letzten Dosierungsform (DFAM< n -i)).Hatchmore Labs GmbH

[0852] 63. System (100) according to embodiment 62, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug tolerance (IDT) by the control device (9) only if the insufficient drug tolerance reaches or is at least a severity level of 2.

[0853] 64. System (100) according to embodiment 62, wherein patient data relating to insufficient drug tolerance (UMV) are taken into account by the control device (9) only if the time of occurrence of insufficient drug tolerance (tuMv) is a time at which the concentration of the drug in the effect compartment (cAM) e ff(tuMv)) at least 50%, preferably at least 60%, such as at least 70%, of the value for the therapeutically effective maximum concentration held in the data storage (M) at that time (at least 0.5 * cAM e ff / MAx(tuMv), preferably at least 0.6 * cAMeff / MAx(tuMv), such as at least 0.7 * cAM e ff / MAx(tuMv)).

[0854] 65. System (100) according to embodiment 64, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug intolerance (ID) by the control device (9) only if the drug intolerance reaches a severity level of at least 1.

[0855] 66. System (100) according to embodiments 1 to 65, wherein the dosage forms of the drug (DFAM) are available as dosage forms with different dose options (such as DOPTION-1 < DOPTION-2 < DOPTION-3), in particular as dosage forms with different discrete dose options, wherein the control device (9) is programmed to select, at the first administration time (tAo) of a dosage form of the drug (DFAMo), not the dose option with the highest dose (DoPTioN-max), and is further programmed to select, at a subsequent administration time (tA n ) to select a dose option from the various, in particular from the various discrete, dose options with a higher dose than the dose option of the time of administration (tAo) (D n > Do) and wherein the control device (9) is programmed to be administered at a further subsequent time (tA) <n+i;) eine Dosisoption mit einer noch höheren Dosis auszuwählen (D< n +1) > D n ), and where patient data concerning the occurrence of insufficient drug tolerance (ID) after the time of administration (tA) n ) are present, these are used when determining the dose of the subsequent dosage form of the drug (DFAM)<n+i;) dahingehend berücksichtigt werden, dass die Dosis D(n+i> ) at the subsequent administration time (tA) <n+i;) im Vergleich zum Verabreichungszeitpunkt (tA n ) is not increased.

[0856] 67. System (100) according to embodiment 66, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug intolerance (IDO) only if the drug intolerance reaches a severity level of at least 2.

[0857] 68. System (100) according to embodiment 66, wherein the electronic control device (9) is programmed to consider patient data relating to insufficient drug tolerance only if the time (tuMv) of the occurrence of insufficient drug tolerance is a time at which the concentration of the drug (cAM) e tf(tuMv)) in a compartment, especially in the effect compartment, is at least 50% of the value for the therapeutically effective maximum concentration (cAMeff / MAx) held in the data storage (M) at that time.

[0858] 69. System (100) according to embodiment 68, wherein the electronic control device (9) is programmed to consider patient data relating to insufficient drug tolerance (IDT) only if the drug intolerance reaches a severity level of at least 1. Hatchmore Labs GmbH

[0859] 70. System (100) according to one of embodiments 66 to 69, wherein the electronic control device (9) is programmed to administer at a further subsequent time (tA< n +y)) again a dose option with a higher dose than that of the following dose option (D< n +i)) to select (D<n+y) > D(n+1>), provided that over a period of at least three consecutive administration times (tA( n +i), tA(n+2> and tA(n+3>), which followed a time point of occurrence of a drug intolerance (tuMv), no further drug intolerance was recorded.

[0860] 71. System (100) according to one of embodiments 66 to 70, wherein a dose option (D n ) is no longer selected if at least three consecutive administration time points (tA) n , tA< n +i) and tA<n+2> ) where the dose option (D n ) was administered, and at least one adverse drug reaction occurred in each case.

[0861] 72. System (100) according to embodiments 1 to 65, wherein the dosage forms of the drug (DFAM) are available as dosage forms with different dose options (such as DOPTION-1 < DOPTION-2 < DOPTION-3 < DoPTioN-max), in particular as dosage forms with different discrete dose options, wherein the electronic control device (9) is programmed not to select the dose option with the lowest dose (DoPTioN-min) at the first administration time (tAo) of a dosage form of the drug (DFAMo), and wherein the electronic control device (9) is programmed at time tAo to select the dosage option with the lowest dose (tA) at a subsequent administration time (tA n ) to select the same dose option (D n = DOPTION-I), and where

[0862] provided that patient data concerning the occurrence of insufficient drug tolerance (ID) after a last administration time (tA< n -i)) are present

[0863] this when determining the dose of the subsequent dosage form of the

[0864] The drug (DFAMn) should be taken into account in such a way that the dose (D n ) at the next administration time (tA n ) compared to the time of administration (tA< n -i)) is reduced.

[0865] 73. System (100) according to embodiment 72, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug intolerance (IDO) only if the drug intolerance reaches a severity level of at least 2.

[0866] 74. System (100) according to embodiment 72, wherein the electronic control device (9) is programmed to consider patient data relating to insufficient drug tolerance only if the time of occurrence of insufficient drug tolerance (tuMv) is a time at which the concentration (cAM) e tf(tuMv)) of the drug (AM) in a compartment, particularly in the effect compartment, is at least 50% of the value for the maximum therapeutic concentration (cAMeff / MAx) held in the data storage (M) at that time.

[0867] 75. System (100) according to embodiment 74, wherein the electronic control device (9) is programmed to consider patient data relating to insufficient drug intolerance (ID) only if the drug intolerance reaches a severity level of at least 1.

[0868] 76. System (100) according to one of embodiments 72 to 75, wherein the electronic control device (9) is programmed to administer at a further subsequent time of administration (tA)<n+x> ) to select a dose option with a higher dose again (D< n +x) > D n ), if over a period of at least three consecutive administration times (tAn, tA< n +i) and tA(n+2>), which followed a time point of onset of a drug intolerance (tuMv), no further drug intolerance was recorded. Hatchmore Labs GmbH

[0869] 77. System (100) according to one of embodiments 72 to 76, wherein the electronic control device (9) is programmed to select a dose option (D n ) no longer selectable if at least three consecutive administration times (tA) n , tA< n +i) and tA(n+2>), where the dose option (D n ) was administered, in each case at least one adverse drug reaction (ADR) occurred.

[0870] 78. System (100) according to one of embodiments 51 to 52, with reference to embodiment 27, wherein the electronic control device (9) is further programmed to include patient data relating to a satisfactory drug effect (ZAMW) when determining the time (tA). n ) and / or the dose (D n ) to take into account the next dosage form (DFAMn) of the drug to be administered to a patient (P), provided that the time of its occurrence (tzAMw) is a time that is after the time of administration of the last dosage form of the drug (tA(ni>) but before the time of the last maximum (tA(ni)max) of the drug concentration cAMeff(tA)<n- i> max) lies, and for which the calculation of the drug concentration in an effect compartment (cAM) is performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M). e ff(tzAMw)) is smaller than the value of a predefined minimum effective concentration in the compartment, especially in the effect compartment (cAMetr / MiN).

[0871] 79. System (100) according to embodiment 78, wherein the electronic control device (9) is further programmed to store the information in the data memory (M) at the time of administration of the last dosage form of the drug (tA< n -i)) to reduce the existing value for the minimum concentration (cAMetr / MiN(tA(ni))),

[0872] provided that the time of onset of a satisfactory drug effect (tzAMw) is a time for which the calculation of the drug concentration in the compartment, in particular in the effect compartment, (cAM) is performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M). e ff(tzAMw)) is smaller than the value stored in the data store (M) at the time of administration of the last dosage form of the drug (tA< n -i)) present value for the minimum concentration (cAMetr / MiN(tA(ni))),

[0873] so that at the time of administration of the next dosage form of the drug (tAn) a value for the minimum concentration (cAM) is stored in the data memory (M). e ff / MiN(tA n )) is present, which is smaller than cAMeff / MiN(tA(ni>).

[0874] 80. System (100) according to embodiment 79, wherein at the time of administration of the next dosage form of the drug (tAn) a value for the minimum concentration (cAM) is stored in the data storage (M). e ff / MiN(tA n )) is present, which corresponds to the calculated value of the drug concentration in the compartment, particularly in the effect compartment, (cAM) at the time of satisfactory drug effect (tzAMw). e ff(tzAMw)) corresponds.

[0875] 81. System (100) according to one of embodiments 51 to 52, with reference to embodiment 27, wherein patient data relating to a satisfactory drug effect (ZAMW) are used to determine the time (tAn) and / or the dose (D). n ) the next dosage form (DFAMn) of the drug to be administered to a patient (P) must be taken into account,

[0876] provided that the time of onset (tzAMw) of satisfactory drug action (ZAMW) is a time that is after the time of administration of the last dosage form of the drug (tA< n -i)), and after the time of the last maximum concentration of the drug (cAMeff(tA(ni)max)), and for which the calculation of the drug concentration in the effect compartment (cAMeff(tzAMw)) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M) is less than the value of a predefined minimum Hatchmore Labs GmbH

[0877] effective concentration in the compartment, especially in the effect compartment (cAMeff / MIN).

[0878] 82. System (100) according to embodiment 81, wherein the electronic control device (9) is programmed to store the information in the data memory (M) at the time of administration of the last dosage form of the drug (tA< n -i)) to reduce the existing value for the minimum concentration (cAMetr / MiN(tA(ni))),

[0879] provided that the time of onset of a satisfactory drug effect (tzAMw) is a time for which the drug concentration in the compartment, in particular the effect compartment (cAMeff(tzAMw)), calculated on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store (M), is lower than the minimum concentration value (cAMeff / MiN(tA(ni))) present in the data store (M) at the time of administration of the last dosage form of the drug (tA(ni>)), such that a minimum concentration value (cAM) is present in the data store (M) at the time of administration of the next dosage form of the drug (tAn). e ff / MiN(tA n )) is present, which is smaller than cAMeff / MiN(tA(ni>).

[0880] 83. System (100) according to embodiment 82, wherein at the time of administration of the next dosage form of the drug (tA) n ) in the data storage (M) a value for the minimum concentration (cAM) e ff / MiN(tA n )) is present, which corresponds to the calculated value of the drug concentration in the compartment, particularly in the effect compartment, (cAM) at the time of satisfactory drug effect (tzAMw). e ff(tzAMw)) corresponds.

[0881] 84. System (100) according to one of the preceding embodiments,

[0882] wherein the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M) include a mathematical relationship between the drug effect and the dose.

[0883] 85. System (100) according to one of the preceding embodiments,

[0884] wherein the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M) include a mathematical relationship between drug side effects and dose.

[0885] 86. System (100) according to embodiment 85 in conjunction with embodiment 84, wherein the electronic control device (9) is programmed to determine the time (tAn) and / or the dose (D) at or during the determination of the time (tAn) and / or the dose (D) n ) to determine or use a value for the clinical benefit of a drug dose from the mathematical relationship between the drug effect and the dose and the mathematical relationship between the drug side effects and the dose of the next dosage form of the drug to be administered to a patient (P).

[0886] 87. System (100) according to embodiment 86, wherein the electronic control device (9) is programmed to determine the dose (D) n ) to determine or use a dose-dependent function for the clinical benefit of a dose from the mathematical relationship between the drug effect and the dose and the mathematical relationship between the drug side effects and the drug dose of the next dosage form of the drug to be administered to a patient (P) (DFAMn).

[0887] 88. System (100) according to embodiment 87, wherein the electronic control device (9) is programmed to select a dose for which the first derivative of a dose-dependent function of the clinical benefit of the drug, after the dose, has a value of at most 0.5, preferably at most 0.4, particularly preferably 0.3. Hatchmore Labs GmbH

[0888] 89. System (100) according to one of embodiments 85 to 88, wherein the electronic control device (9) is programmed to select from among various possible dose options the dose option (Dx) for which the value of the dose-dependent function for clinical benefit is highest.

[0889] 90. System (100) according to one of embodiments 1 to 52, wherein the dosage forms of the drug product (DFAM) are available as dosage forms with different dose options (such as DOPTION-1 < DOPTION-2 < DOPTION-3), in particular as dosage forms with different discrete dose options, wherein the next administration time (tA) n ) a dosage form of the drug (DFAMn) to the next administration time (tA) n ) preceding pretreatment period with a final administration time (tA< n -i)) follows, in which the lowest dose option (DoPTioN-min) was not selected, and wherein the electronic control device (9) at time (tA< n -i)) is further programmed to select a dose option with a lower dose at the next administration time (tAn) (D n < D n -i), and wherein patient data relating to insufficient drug tolerance (IDT), which after the time (tA <n-i>) occur, when determining the dose of the subsequent dosage form of the drug, in such a way that the dose at the next administration time (tAn) is adjusted in comparison to the administration time (tA). <n-i>) but it is not reduced.

[0890] 91. System (100) according to embodiment 90, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug intolerance (IDO) only if the drug intolerance reaches a severity level of at least 2.

[0891] 92. System (100) according to embodiment 90, wherein the electronic control device (9) is programmed to consider patient data relating to insufficient drug tolerance only if the time of occurrence of insufficient drug tolerance (tuMv) is a time at which the concentration of the drug in a compartment, in particular in the effect compartment, (cAM) e ff(tuMv)) is at most 50% of the concentration of the last maximum of the drug concentration (cAMeff(tA(ni)max)).

[0892] 93. System (100) according to embodiment 92, wherein the electronic control device (9) is programmed to take into account patient data relating to insufficient drug intolerance (ID) only if the drug intolerance reaches a severity level of at least 1.

[0893] 94. System (100) according to one of embodiments 90 to 93, wherein the electronic control device (9) is programmed to administer the next dosage form (D) at a time after the next time (tAn). n ) time of administration (tA)<n+2+x> ) again a dose option with a lower dose than that of the next dosage form (D n ) to select (D< n +2+x) < D n ),

[0894] provided that over a period of at least three consecutive administration times (tA) n , tA< n +i) and tA(n+2>), which followed a time point of occurrence of a drug intolerance (tuMv), no further drug intolerance was recorded.

[0895] 95. System (100) according to one of embodiments 1 to 89, wherein the dosage forms of the drug (DFAM) are available as dosage forms with different dose options (such as DOPTION-1 < DOPTION-2 < DOPTION-3), in particular as dosage forms with different discrete dose options, wherein the next administration time (tAn) of a dosage form of the drug (DFAMn) is based on a pretreatment period with a last administration time (tA). <n-i>) follows, in which the lowest dose option (DoPTioN-min) was not selected, and wherein the electronic control device (9) at time (tA <n-i>) is programmed to select a dose option with the same dose at the next administration time (tAn) (D n = D(n-1>), where the administration times are at defined time points. Hatchmore Labs GmbH

[0896] take place,

[0897] where patient data concerning a lack of medication intake at the last intended administration time (tA< n -i)) when determining the dose (D n ) the next dosage form of the drug (DFAMn) should be taken into account in such a way that the dose at the next administration time (tA) n ) compared to the time of administration (tA< n -i)) is increased.

[0898] 96. System (100) according to one of embodiments 40 to 95, wherein the patient has the choice to take the dosage forms of the medicinal product (DFAM) at one or more administration times per unit of time, in particular per day.

[0899] 97. System (100) according to embodiment 96, wherein the dispensing device (17) is available to the patient (P) from the next administration time (tA) n ) an increase or decrease in the number of administration times per unit of time compared to the number of administration times per the same unit of time at the last administration time (tA< n -i)) is stored, suggests.

[0900] 98. System (100) according to one of embodiments 55 or 56, wherein the output device (17) indicates the time at which the minimum concentration (cAMetr / MiN) is reached and / or falls below the minimum concentration.

[0901] 99. System (100) according to embodiment 98, wherein the dispensing device (17) requests administration of the drug (D) before the time at which the minimum concentration (cAMeff / MiN) is reached and / or falls below the minimum concentration (cAMeff / MiN). 100. System (100) according to any one of embodiments 52 to 99, wherein a reference to the drug (D) is replaced by a reference to the active metabolite of the drug (AMB).

[0902] 101. System (100) according to one of embodiments 52 to 99, wherein a reference to the drug (D) is to be replaced by a reference to the drug (D) and the active metabolite of the drug (MB).

[0903] 102. System (100) according to one of embodiments 52 to 99, wherein a reference to the drug (D) is to be replaced by a reference to the weighted sum of the drug (D) and the active metabolite (AMB) of the drug.

[0904] 103. System (100) according to embodiment 102, wherein the weighting between drug (D) and the active metabolite of the drug (MB) is based on their respective efficacy.

[0905] 104. System (100) according to embodiment 102, wherein the weighting between drug (D) and the active metabolite of the drug (MB) is based on the severity of their respective side effects.

[0906] 105. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the bioavailability of a drug (D) in the given dosage form (DFDD) present in the data storage (M) at the beginning of treatment of a patient (P) is changed for the further treatment of the same patient (P) if the observed pharmacokinetics of the drug (D) in this patient (P) suggest that the value for the bioavailability of the drug (D) present in the data storage (M) at the beginning of treatment of the patient (P) does not correctly describe the individual bioavailability of the drug (D) in the patient (P).

[0907] 106. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the data storage device (M) at the beginning of the treatment of a patient (P) is Hatchmore Labs GmbH

[0908] The existing value for the volume of distribution of the drug (AM) for further treatment of the same patient (P) is changed if the observed pharmacokinetics of the drug in this patient (P) suggest that the value for the volume of distribution of the drug (AM) present in the data store at the start of a patient's treatment does not correctly describe the individual volume of distribution of the drug (AM) in the patient (P).

[0909] 107. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the electronic control device (9) is programmed to change the value for the time-to-peak concentration (tmax(AM)) of the drug (AM) present in the data storage (M) at the beginning of the patient's (P) treatment for the further treatment of the same patient (P) if the observed pharmacokinetics of the drug (AM) in this patient (P) suggest that the value for the time-to-peak concentration (tmax(AM)) of the drug present in the data storage (M) at the beginning of the patient's (P) treatment does not correctly describe the individual time-to-peak concentration (tmax(AM>)) of the drug (AM) in the patient.

[0910] 108. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the half-life of the drug in a compartment of the body, such as the half-life of the drug in the blood and in particular the blood plasma half-life, which is present in the data storage at the beginning of a patient's treatment, is changed for the further treatment of the same patient if the observed pharmacokinetics of the drug in that patient are expected to be the individual half-life of the drug in a compartment of the body, such as the half-life of the drug in the blood and in particular the blood plasma half-life, which is present in the data storage at the beginning of a patient's treatment.such as not correctly describing the individual half-life of the drug in the blood and, in particular, the individual blood plasma half-life in the patient.

[0911] 109. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the drug clearance value stored in the data storage at the start of a patient's treatment is modified for the further treatment of the same patient if the observed pharmacokinetics of the drug in that patient suggest that the drug clearance value stored in the data storage at the start of a patient's treatment does not accurately describe the individual drug clearance in the patient.

[0912] 110. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the volume of distribution of an active metabolite of the drug present in the data storage at the beginning of treatment of a patient is changed for the further treatment of the same patient if the observed pharmacokinetics of the active metabolite of the drug in that patient suggest that the value for the volume of distribution of the active metabolite of the drug present in the data storage at the beginning of treatment of a patient does not correctly describe the individual volume of distribution of the active metabolite of the drug in the patient.

[0913] 111. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the time-to-peak concentration (tmax (AMB>)) of an active metabolite of the drug present in the data storage at the beginning of treatment of a patient is changed for the further treatment of the same patient if the observed pharmacokinetics of the active metabolite of the drug in this Hatchmore Labs GmbH

[0914] This leads patients to expect that the value for the “time-to-peak concentration” (tmax(AMB>) of the active metabolite of the drug, which is present in the data storage at the start of a patient’s treatment, does not correctly describe the individual “time-to-peak concentration” (tmax(AMB>) of the active metabolite of the drug in the patient.

[0915] 112. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value stored in the data storage at the beginning of a patient's treatment for the half-life of the active metabolite of the drug in a compartment of the body, such as the half-life of the active metabolite of the drug in the blood and, in particular, the blood plasma half-life of an active metabolite of the drug, is changed for the further treatment of the same patient if the observed pharmacokinetics of the drug in that patient are expected to change the value stored in the data storage at the beginning of a patient's treatment for the active metabolite of the drug in a compartment of the body.such as the half-life of the drug's active metabolite in the blood, and in particular the blood plasma half-life of the drug's active metabolite, or the individual half-life of the drug's active metabolite in a compartment of the body, such as the individual half-life of the drug's active metabolite in the blood, and in particular the individual blood plasma half-life of the drug's active metabolite in the patient, does not correctly describe the individual half-life of the drug's active metabolite in the blood, and in particular the individual blood plasma half-life of the drug's active metabolite in the patient.

[0916] 113. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the clearance of an active metabolite of the drug present in the data storage at the beginning of treatment of a patient is changed for the further treatment of the same patient if the observed pharmacokinetics of the drug in that patient suggest that the value for the clearance of the active metabolite of the drug present in the data storage at the beginning of treatment of a patient does not correctly describe the individual clearance of the active metabolite of the drug in the patient.

[0917] 114. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the therapeutic maximum concentration (cAMetf / MAx) of the drug (AM) in the effect compartment present in the data storage (M) at the beginning of treatment of a patient (P) is changed for the further treatment of the same patient (P) if the observed pharmacodynamics of the drug in this patient (P) suggests that the value for the therapeutic maximum concentration (cAMetf / MAx) present in the data storage at the beginning of treatment of a patient will be changed.

[0918] The maximum concentration (cAMeff / MAx) of the drug (AM) in the effect compartment does not correctly describe the individual value for the maximum therapeutic concentration (cAMetf / MAx) of the drug (AM) in the effect compartment in the patient (P).

[0919] 115. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the value for the minimum therapeutically effective concentration of the drug (cAMetr / MiN) in the effect compartment present in the data storage (M) at the beginning of treatment of a patient (P) is changed for the further treatment of the same patient (P) if the observed pharmacodynamics of the drug in this patient (P) suggest that the value for the minimum therapeutically effective concentration of the drug (cAMeff / MiN) in the effect compartment present in the data storage at the beginning of treatment of a patient does not correctly describe the individual value for the minimum therapeutically effective concentration of the drug (cAMetr / MiN) in the effect compartment in the patient (P). Hatchmore Labs GmbH

[0920] 116. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the dose-response relationship (DR) present in the data storage (M) at the beginning of treatment of a patient (P) is modified for the further treatment of the same patient (P) if the observed pharmacodynamics of the drug in this patient (P) suggests that the dose-response relationship (DR) present in the data storage at the beginning of treatment of a patient does not correctly describe the individual dose-response relationship (DR) for the patient (P).

[0921] 117. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the dose-exposure relationship (DE) present in the data storage (M) at the beginning of treatment of a patient (P) is modified for the further treatment of the same patient (P) if the observed pharmacodynamics of the drug in this patient (P) suggests that the dose-exposure relationship (DE) present in the data storage at the beginning of treatment of a patient does not correctly describe the individual dose-exposure relationship (DE) for the patient (P).

[0922] 118. System (100) according to one of embodiments 12 to 104, each referring back to embodiment 8, embodiment 9, embodiment 10 and / or embodiment 11, wherein the dose-exposure-response relationship (DER) present in the data storage (M) at the beginning of treatment of a patient (P) is modified for the further treatment of the same patient (P) if the observed pharmacodynamics of the drug in this patient (P) suggests that the dose-exposure-response relationship (D-ER) present in the data storage at the beginning of treatment of a patient does not correctly describe the individual dose-exposure-response relationship (DER) for the patient (P).

[0923] MU1. A medicinal product for use or application in the treatment of a disease, wherein the medicinal product is a component of a system and the system is designed to determine the time and / or dose of the medicinal product (AM) to be administered to a patient (P), and wherein the system (100) further comprises the following functional components, namely

[0924] an electronic control device (9);

[0925] a data storage device (M) for storing at least

[0926] of administration times (tAo, tAi, tA2,..., tA(ni>) of one or more previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)) and / or the dose (Do, Di, D2,..., D(ni>) of these previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni));

[0927] a feedback device (8) for recording patient data relating to the patient's response to administration of a dosage form of the medicinal product (DFAM);

[0928] wherein the electronic control device (9) is further programmed to

[0929] Reading data stored in the data storage (M);

[0930] Evaluating the patient data acquired by the feedback device (8); and to

[0931] Determining the time (tA) n , tA< n +i), tA< n +2),..., tA(n+x>) and / or the dose (D n , D(n+i;, D(n+2>,..., D(n+x>) for the administration of the next or further dosage form(s) of the medicinal product (DFAMn, DFAM<n+i), DFAM(n+2> ,..., DFAM(n+x>) taking into account the read and recorded data; Hatchmore Labs GmbH

[0932] an output device, in particular an information output device (17), for outputting information at the determined time(s) (tA n , tA< n +i), tA(n+2>,..., tA(n+x>) and / or the determined dose (D n , D<n+1), D(n+2),..., D(n+x> ) concerning the next or further dosage form(s) of the medicinal product (DFAM), or for dispensing the next or further dosage form(s) of the medicinal product (DFAM).

[0933] MU2. A medicinal product for use or application in the treatment of a disease, wherein the time and / or dose of the next dosage form of the medicinal product to be administered to a patient is determined by an electronic control device, by

[0934] a feedback device (8) records patient data concerning the patient's response to the last administration of a dosage form of the medicinal product (DFAM); the electronic control device reads from a data storage device data concerning administration times (tAo, tAi, tA2,..., tA(ni>) of one or more previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)) and / or concerning the dose (Do, Di, D2,..., D(n-1>) of these previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni));

[0935] the electronic control device reads pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP) from the data storage device (M);

[0936] and wherein the electronic control device takes into account the patient data relating to the patient's response to the last administration, the data relating to the administration times and / or the last dose, and the data relating to the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP) when determining the next time and / or the next dose of the dosage form to be administered to a patient.

[0937] MU 3. A medicinal product for use or application in the treatment of a disease, wherein the timing and / or dose of the next dosage form of the medicinal product to be administered to a patient is / are determined by relating the timing and / or extent of a patient's response to the last administered dosage form of the medicinal product to the calculation of the concentration of the medicinal product in an effect compartment at that time, wherein the calculation of the concentration of the medicinal product is based on pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP).

[0938] MU 4. A medicinal product for use or application in the treatment of a disease, wherein a dosage form of the medicinal product is administered at a specific time and with a specific dose, and wherein

[0939] the timing and / or dose of the next dosage form of the medicinal product to be administered to a patient is determined, whereby the timing and / or extent of a patient's response to the last administered dosage form of the medicinal product is related to the calculation of the concentration of the medicinal product in an effect compartment at that time, and wherein the calculation of the concentration of the medicinal product is based on pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP).

[0940] MU 5. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a drug of ATC class A and the disease is a disease of the digestive tract or a metabolic disorder.

[0941] MU 6. The medicinal product according to embodiment MU 5, wherein the medicinal product is a medicinal product of ATC class A07 and the disease is a disease of the digestive tract. Hatchmore Labs GmbH

[0942] MU 7. The medicinal product according to embodiment MU 6, wherein the medicinal product is a medicinal product of ATC class A07D, for the treatment of diarrheal diseases.

[0943] MU 8. The medicinal product according to embodiment MU 5, wherein the medicinal product is a medicinal product from ATC class A08, for the treatment of overweight and / or for weight control and / or for weight reduction.

[0944] MU 9. The medicinal product according to embodiment MU 8, wherein the medicinal product is a medicinal product of ATC class A08A, for the treatment of obesity

[0945] MU 10. The medicinal product according to embodiment MU 5, wherein the medicinal product is a medicinal product from ATC class A10, in particular from class A10B, for the treatment of diabetes.

[0946] MU 11. The medicinal product according to embodiment MU 5, wherein the medicinal product is a medicinal product of ATC class A16, in particular of class A16A, for the treatment of a disease of the digestive tract or for the treatment of a metabolic disorder.

[0947] MU 12. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a drug of ATC class B and the disease is a disease of the blood or the hematopoietic system.

[0948] MU 13. The medicinal product according to embodiment MU 12, wherein the medicinal product is a medicinal product of ATC class B01, in particular of class B01A, for the treatment and / or prophylaxis of thrombosis.

[0949] MU 14. The medicinal product according to embodiment MU 12, wherein the medicinal product is a medicinal product of ATC class B02, in particular of class B02B, for the treatment and / or prophylaxis of bleeding.

[0950] MU 15. The medicinal product according to embodiment MU 14, wherein the medicinal product is a medicinal product of ATC class B02B, in particular as an antidote to anticoagulants for the treatment and / or prophylaxis of bleeding.

[0951] MU 16. The medicinal product according to embodiment MU 12, wherein the medicinal product is a medicinal product of ATC class B03, for the treatment of anemia.

[0952] MU 17. The medicinal product according to embodiment MU 16, wherein the medicinal product is a medicinal product of ATC class B03X.

[0953] MU 18. The medicinal product according to embodiment MU 12, wherein the medicinal product is a medicinal product of ATC class B05.

[0954] MU 19. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class C and the disease is a disease of the cardiovascular system.

[0955] MU 20. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product of ATC class C01, in particular of class C01B, and the disease is a disease of the heart.

[0956] MU 21. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product of ATC class CO2, for the treatment of hypertension.

[0957] MU 22. The medicinal product according to embodiment MU 21, wherein the medicinal product is a medicinal product of ATC class C02K.

[0958] MU 23. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product of ATC class C03, in particular of class C03X, for increasing urine production. Hatchmore Labs GmbH

[0959] MU 24. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product of ATC class C07, in particular for the treatment of hypertension, for the treatment of angina pectoris, for the treatment of coronary artery disease, for the treatment of migraine and / or for the treatment of cardiac arrhythmia.

[0960] MU 25. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product of ATC class C09, in particular for the treatment of hypertension, for the treatment of coronary artery disease, for the treatment of the condition after a heart attack, for the treatment of migraine and / or for the treatment of chronic kidney disease.

[0961] MU 26. The medicinal product according to embodiment MU 19, wherein the medicinal product is a medicinal product from ATC class C10, in particular from class C10A or C1OB, especially for the treatment of hypercholesterolemia.

[0962] MU 27. The medicinal product according to embodiment MU 26, wherein the medicinal product is from ATC class C10AA, C10AB, C10AD or C10AX.

[0963] MU 28. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class D and the disease is a disease of the skin.

[0964] MU 29. The medicinal product according to embodiment MU 28, wherein the medicinal product is a medicinal product of ATC class D07, in particular for the treatment of eczema, psoriasis, dermatitis, allergic skin reactions and / or inflammation of the skin.

[0965] MU 30. The medicinal product according to embodiment MU 29, wherein the medicinal product is a medicinal product of ATC class D07A.

[0966] MU 31. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class D11, in particular for the treatment of hypertension, for the treatment of angina pectoris and / or for the treatment of a skin disease.

[0967] MU 32. The medicinal product according to any embodiment MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class G01, for the treatment of vaginal infections. MU 33. The medicinal product according to any embodiment MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class G03, for contraception.

[0968] MU 34. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class H and the disease is a systemic hormonal disorder.

[0969] MU 35. The medicinal product according to embodiment MU 34, wherein the medicinal product is a medicinal product of ATC class H01, in particular of class H01A or H01C, and the hormonal disorder involves pituitary and / or hypothalamic hormones.

[0970] MU 36. The medicinal product according to embodiment MU 34, wherein the medicinal product is a medicinal product of ATC class H03, in particular of class H03A, and relates to the hormonal disorder of thyroid hormones.

[0971] MU 37. The medicinal product according to embodiment MU 34, wherein the medicinal product is a medicinal product of ATC class H05, in particular of class H05B, and relates to the hormonal disorder of parathyroid hormones.

[0972] MU 38 The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class J01, as an antibiotic. Hatchmore Labs GmbH

[0973] MU 39. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class J05, as an antiviral agent.

[0974] MU 40. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class L and the disease is a cancer or an autoimmune disease.

[0975] MU 41. The medicinal product according to embodiment MU 40, wherein the medicinal product is a medicinal product of ATC class L01 and the disease is cancer.

[0976] MU 42. The medicinal product according to embodiment MU 41, wherein the medicinal product is a medicinal product from ATC class L01A, L01B, L01C, L01E, L01F or L01X.

[0977] MU 43. The medicinal product according to embodiment MU 41, wherein the medicinal product is a medicinal product from ATC class L01 AA, L01 BC, L01 DB, L01 EA, L01 EB, L01 EC, L01 ED, L01 EE, L01 EF, L01EG, L01EH, L01EJ, L01EK, L01EL, L01 EM, L01EN, L01EX, L01FA, L01FX, L01XG, L01XK or L01XX.

[0978] MU 44. The medicinal product according to embodiment MU 40, wherein the medicinal product is a medicinal product of ATC class L04, for the treatment of autoimmune diseases or for the prevention of organ rejection in organ transplantation.

[0979] MU 45. The medicinal product according to embodiment MU 44, wherein the medicinal product is a medicinal product of ATC class L04A.

[0980] MU 46. The medicinal product according to embodiment MU 45, wherein the medicinal product is a medicinal product from ATC class L04AD, L04AE, L04AF or L04AX.

[0981] MU 47. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class N and the disease is a disease of the nervous system.

[0982] MU 48. The medicinal product according to embodiment MU 47, wherein the medicinal product is a medicinal product of ATC class N01, for pain prevention.

[0983] MU 49. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class N02, for the treatment of pain.

[0984] MU 50. The medicinal product according to embodiment MU 47, wherein the medicinal product is a medicinal product of ATC class N03, in particular of class N03A, for the treatment of epilepsy. MU 51. The medicinal product according to embodiment MU 47, wherein the medicinal product is a medicinal product of ATC class N05, for the treatment of mental disorders, in particular for the treatment of anxiety, depression, psychoses and / or schizophrenia.

[0985] MU 52. The medicinal product according to embodiment MU 51, wherein the medicinal product is a medicinal product of ATC class N05A, for the treatment of psychoses.

[0986] MU 53. The medicinal product according to embodiment MU 51, wherein the medicinal product is a medicinal product of ATC class N05B, for the treatment of anxiety disorders.

[0987] MU 54. The medicinal product according to embodiment MU 51, wherein the medicinal product is a medicinal product of ATC class N05C, for the treatment of sleep disorders or anxiety. MU 55. The medicinal product according to embodiment MU 47, wherein the medicinal product is a medicinal product of ATC class N06, for the stimulation of the activity of the central nervous system, in particular for increasing the ability to concentrate, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy. Hatchmore Labs GmbH

[0988] MU 56. The medicinal product according to embodiment MU 55, wherein the medicinal product is from ATC class N06A, for the treatment of depression.

[0989] MU 57. The medicinal product according to embodiment MU 55, wherein the medicinal product is from ATC class N06B, for the treatment of ADHD, narcolepsy and / or dementia.

[0990] MU 58. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class P01B, for the treatment of malaria.

[0991] MU 59. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class R and the disease is a disease of the respiratory system.

[0992] MU 60. The medicinal product according to embodiment MU 59, wherein the medicinal product is a medicinal product of ATC class R01, for nasal administration.

[0993] MU 61. The medicinal product according to embodiment MU 59, wherein the medicinal product is a medicinal product of ATC class R03, for the treatment of an obstructive airway disease.

[0994] MU 62. The medicinal product according to embodiment MU 59, wherein the medicinal product is a medicinal product of ATC class R05, for the treatment of cough and / or cold symptoms. MU 63. The medicinal product according to embodiment MU 59, wherein the medicinal product is a medicinal product of ATC class R07, for the treatment of respiratory insufficiency and / or for stimulating respiratory activity.

[0995] MU 64. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class S and the disease is a disease of the sensory organs.

[0996] MU 65. The medicinal product according to embodiment MU 64, wherein the medicinal product is a medicinal product of ATC class S01, for the treatment of a disease of the eye.

[0997] MU 66. The medicinal product according to embodiment MU 64, wherein the medicinal product is a medicinal product of ATC class S02, for the treatment of a disease of the ear.

[0998] MU 67. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product is a medicinal product of ATC class V03AB, V03AC, V03AE or V03AF.

[0999] MU 68. The medicinal product according to embodiment MU 67, wherein the medicinal product is a medicinal product of ATC class V03AB, for the treatment of poisoning.

[1000] MU 69. The medicinal product according to embodiment MU 67, wherein the medicinal product is a medicinal product of ATC class V03AC, for the treatment of a disorder of iron metabolism.

[1001] MU 70. The medicinal product according to embodiment MU 67, wherein the medicinal product is a medicinal product of ATC class V03AE, for the treatment of hyperkalemia or hyperphosphatemia. MU 71. The medicinal product according to embodiment MU 67, wherein the medicinal product is a medicinal product of ATC class V03AF, for the treatment of symptoms of poisoning.

[1002] MU 72. The medicinal product according to any of the embodiments MU1 to MU 4, wherein the medicinal product interacts with a drug target and the drug target is selected from the group consisting of enzymes, receptors, transporters, ion channels, structural proteins, binding proteins, regulatory proteins, proteins of the immune system, proteins of the coagulation cascade and cell adhesion proteins.

[1003] MU 73. The drug according to embodiment MU 72, wherein the drug target is P00533 [UniProt ID], for the treatment of cancer. Hatchmore Labs GmbH

[1004] MU 74. The drug according to embodiment MU 72, wherein the drug target is P01375 [UniProt ID], for the treatment of an autoimmune disease.

[1005] MU 75. The drug according to embodiment MU 72, wherein the drug target is P04626 [UniProt ID], for the treatment of cancer.

[1006] MU 76. The drug according to embodiment MU 72, wherein the drug target is P15692 [UniProt ID], for the treatment of cancer and / or for the treatment of macular degeneration. MU 77. The drug according to embodiment MU 72, wherein the drug target is P00519 [UniProt ID], for the treatment of cancer.

[1007] MU 78. The drug according to embodiment MU 72, wherein the drug target is P11836 [UniProt ID], for the treatment of cancer and / or an autoimmune disease.

[1008] MU 79. The drug according to embodiment MU 72, wherein the drug target is Q15116 [UniProt ID], for the treatment of cancer.

[1009] MU 80. The drug according to embodiment MU 72, wherein the drug target is P16410 [UniProt ID], for the treatment of cancer.

[1010] MU 81. The drug according to embodiment MU 72, wherein the drug target is P07550 [UniProt ID], for the treatment of a respiratory disease.

[1011] MU 82. The drug according to embodiment MU 72, wherein the drug target is P07437 [UniProt ID], for the treatment of cancer.

[1012] MU 83. The drug according to embodiment MU 72, wherein the drug target is P00451 [UniProt ID], for the treatment of hemophilia.

[1013] MU 84. The drug according to embodiment MU 72, wherein the drug target is P00734 [UniProt ID], for the treatment of hemophilia.

[1014] MU 85. The drug according to embodiment MU 72, wherein the drug target is P04150 [UniProt ID], for the treatment of a disorder of the immune system.

[1015] MU 86. The drug according to embodiment MU 72, wherein the drug target is P04818 [UniProt ID], for the treatment of cancer.

[1016] MU 87. The drug according to embodiment MU 72, wherein the drug target is P08581 [UniProt ID], for the treatment of cancer.

[1017] MU 88. The drug according to embodiment MU 72, wherein the drug target is P08588 [UniProt ID], for the treatment of hypertension.

[1018] MU 89. The drug according to embodiment MU 72, wherein the drug target is P09874 [UniProt ID], for the treatment of cancer.

[1019] MU 90. The drug according to embodiment MU 72, wherein the drug target is P10827 [UniProt ID], for the treatment of a hormonal disorder.

[1020] MU 91. The drug according to embodiment MU 72, wherein the drug target is P11802 [UniProt ID], for the treatment of cancer.

[1021] MU 92. The drug according to embodiment MU 72, wherein the drug target is P14416 [UniProt ID], for the treatment of a mental disorder, in particular for the treatment of anxiety, depression, psychosis and / or schizophrenia. Hatchmore Labs GmbH

[1022] MU 93. The drug according to embodiment MU 72, wherein the drug target is P14867 [UniProt ID], for the treatment of epilepsy and / or a mental disorder, in particular for the treatment of anxiety, depression, psychosis and / or schizophrenia.

[1023] MU 94. The drug according to embodiment MU 72, wherein the drug target is P15056 [UniProt ID], for the treatment of cancer.

[1024] MU 95. The drug according to embodiment MU 72, wherein the drug target is P23458 [UniProt ID], for the treatment of an autoimmune disease.

[1025] MU 96. The drug according to embodiment MU 72, wherein the drug target is P28223 [UniProt ID], for the treatment of mental disorders, in particular for the treatment of anxiety, depression, psychoses and / or schizophrenia.

[1026] MU 97. The drug according to embodiment MU 72, wherein the drug target is P30556 [UniProt ID], for the treatment of hypertension, for the treatment of coronary artery disease, for the treatment of the condition following a myocardial infarction, for the treatment of migraine and / or for the treatment of chronic kidney disease.

[1027] MU 98. The drug according to embodiment MU 72, wherein the drug target is P31639 [UniProt ID], for lowering blood glucose levels.

[1028] MU 99. The drug according to embodiment MU 72, wherein the drug target is P31645 [UniProt ID], for stimulating the activity of the central nervous system, in particular for increasing concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[1029] MU 100. The drug according to embodiment MU 72, wherein the drug target is P35372 [UniProt ID], for the treatment of a disease of the nervous system and / or for the treatment of pain.

[1030] MU 101. The drug according to embodiment MU 72, wherein the drug target is P35498 [UniProt ID], for the treatment of epilepsy.

[1031] MU 102. The drug according to embodiment MU 72, wherein the drug target is P35968 [UniProt ID], for the treatment of cancer.

[1032] MU 103. The drug according to embodiment MU 72, wherein the drug target is P36888 [UniProt ID], for the treatment of cancer.

[1033] MU 104. The drug according to embodiment MU 72, wherein the drug target is P42345 [UniProt ID], for the treatment of cancer.

[1034] MU 105. The drug according to embodiment MU 72, wherein the drug target is P43119 [UniProt ID], for the treatment of pulmonary (arterial) hypertension.

[1035] MU 106. The drug according to embodiment MU 72, wherein the drug target is Q01959 [UniProt ID], for stimulating the activity of the central nervous system, in particular for increasing concentration, for the treatment of ADHD, for the treatment of depression and / or for the treatment of narcolepsy.

[1036] MU 107. The drug according to embodiment MU 72, wherein the drug target is Q02750 [UniProt ID], for the treatment of cancer.

[1037] MU 108. The drug according to embodiment MU 72, wherein the drug target is Q06187 [UniProt ID], for the treatment of cancer.

[1038] MU 109. The drug according to embodiment MU 72, wherein the drug target is Q7L0J3 [UniProt ID], for the treatment of epilepsy. Hatchmore Labs GmbH

[1039] MU 110. The drug according to embodiment MU 72, wherein the drug target is Q96SW2 [UniProt ID], for the treatment of cancer.

[1040] MU 111. The drug according to embodiment MU 72, wherein the drug target is Q9GZT9 [UniProt ID], for the treatment of anemia.

[1041] MU 112. The drug according to embodiment MU 72, wherein the drug target is Q9UM73 [UniProt ID], for the treatment of cancer.

[1042] MU 113. The drug according to embodiment MU 72, wherein the Drug Target is 000329 [UniProt ID], for the treatment of cancer.

[1043] MU 114. The drug according to embodiment MU 72, wherein the Drug Target is 075874 [UniProt ID], for the treatment of cancer.

[1044] MU 115. The drug according to embodiment MU 72, wherein the drug target is P00374 [UniProt ID], for the treatment of cancer and / or for the treatment of an autoimmune disease.

[1045] MU 116. The medicinal product according to embodiment MU 72, wherein the drug target is P00742 [UniProt ID], for the treatment and / or prophylaxis of thrombosis or for the treatment of hemophilia A.

[1046] MU 117. The drug according to embodiment MU 72, wherein the drug target is P01008 [UniProt ID], for the treatment and / or prophylaxis of thrombosis.

[1047] MU 118. The drug according to embodiment MU 72, wherein the drug target is P01116 [UniProt ID], for the treatment of cancer.

[1048] MU 119. The drug according to embodiment MU 72, wherein the drug target is P03372 [UniProt ID], for the treatment of cancer.

[1049] MU 120. The drug according to embodiment MU 72, wherein the drug target is P04035 [UniProt ID], for the treatment of hypercholesterolemia.

[1050] MU 121. The drug according to embodiment MU 72, wherein the drug target is P04629 [UniProt ID], for the treatment of cancer.

[1051] MU 122. The drug according to embodiment MU 72, wherein the drug target is P06401 [UniProt ID], for the prevention of pregnancy in women.

[1052] Drug Target

[1053] MU 123. The drug according to embodiment MU 72, wherein the drug target is P07949 [UniProt ID], for the treatment of cancer.

[1054] MU 124. The drug according to embodiment MU 72, wherein the drug target is P08235 [UniProt ID], for increasing urine production.

[1055] MU 125. The drug according to embodiment MU 72, wherein the drug target is P08908 [UniProt ID], for the treatment of depression.

[1056] MU 126. The drug according to embodiment MU 72, wherein the drug target is P10275 [UniProt ID], for the treatment of cancer.

[1057] MU 127. The drug according to embodiment MU 72, wherein the drug target is P10276 [UniProt ID], for the treatment of a skin disease.

[1058] MU 128. The drug according to embodiment MU 72, wherein the drug target is P10415 [UniProt ID], for the treatment of cancer. Hatchmore Labs GmbH

[1059] MU 129. The drug according to embodiment MU 72, wherein the drug target is P10721 [UniProt ID], for the treatment of cancer.

[1060] MU 130. The drug according to embodiment MU 72, wherein the drug target is P11229 [UniProt ID], for the treatment of a disorder of the digestive tract and / or a disorder of bladder function.

[1061] MU 131. The drug according to embodiment MU 72, wherein the drug target is P11362 [UniProt ID], for the treatment of cancer.

[1062] MU 132. The drug according to embodiment MU 72, wherein the drug target is P11388 [UniProt ID], for the treatment of cancer.

[1063] MU 133. The drug according to embodiment MU 72, wherein the drug target is P11473 [UniProt ID], for the treatment of a systemic hormonal disorder.

[1064] MU 134. The drug according to embodiment MU 72, wherein the drug target is P12821 [UniProt ID], for the treatment of hypertension, for the treatment of coronary artery disease, for the treatment of the condition following a myocardial infarction, for the treatment of migraine and / or for the treatment of chronic kidney disease.

[1065] MU 135. The drug according to embod...

Claims

Hatchmore Labs GmbH Claims 1. System (100) for determining the time and / or dose of a drug (D) to be administered to a patient (P), the system (100) comprising, or consisting of, the following functional components, an electronic control device (9); a data storage device (M) for storing at least of administration times (tAo, tAi, tA2,..., tA(ni>) of one or more previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)) and / or the dose (Do, Di, D2,..., D(ni>) of these previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)); of numerical values, where the numerical values ​​describe: o which concentration of the drug (D) and / or an active metabolite (MB) of the drug (D) is attributed to a desired drug effect; and o which concentration of the drug (D) and / or an active metabolite (MB) of the drug (D) is attributed to an adverse drug reaction; and / or o what proportion of the medicinal product (MP) from a given dosage form of the medicinal product (DFMP) is absorbed by the body; and / or o how the medicinal product (MP) is distributed in the body; and / or how long it takes for the concentration of the drug (D) in a compartment of the body, such as the blood, and especially the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM); and / or how long it takes for the concentration of an active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM); and / or how quickly the concentration of the drug (AM) in a compartment of the body, such as the blood, and in particular the blood plasma, decreases per unit of time; and / or how quickly the concentration of an active metabolite of the drug (AMB) decreases in a compartment of the body, such as the blood, and especially the blood plasma, per unit of time; and / or what amount of the drug (AM) is eliminated from the body per unit of time; and / or o the amount of an active metabolite of the drug (AMB) that is excreted from the body per unit of time; where the numerical value describing the concentration of a drug (D) that is assigned to a desired drug effect is a therapeutically effective minimum concentration of the drug in an effect compartment (cAMetr / MiN); and / or where the numerical value describes the concentration of Hatchmore Labs GmbH The active metabolite of the drug (AMB) is assigned to a desired drug effect, and the therapeutically effective minimum concentration of the active metabolite of the drug in an effect compartment (cAMBeff / MiN) is defined as: where the numerical value describing the concentration of the drug (D) associated with an adverse drug reaction is a therapeutically acceptable maximum concentration of the drug in an effect compartment (cAMetf / MAx); and / or where the numerical value describing the concentration of the drug's active metabolite (AMB) associated with an adverse drug reaction is a therapeutically acceptable maximum concentration of the active metabolite in an effect compartment (cAMBeff / MAx); a feedback device (8) for recording patient data relating to the patient's response to administration of a dosage form of the medicinal product (DFAM); a writing device (13) programmed to write or overwrite one or more or all of the numerical values ​​in the data memory (M) during a treatment, wherein the control device (9) or the writing device is programmed to individualize one or more or all of the numerical values ​​for the patient (P) during a treatment; wherein the electronic control device (9) is further programmed to Reading data stored in the data storage device (M); evaluating patient data acquired by the feedback device (8); and for Determining the time (tA) n , tA< n +i), tA< n +2),..., tA(n+x>) and / or the dose (D n , D(n+i;, D(n+2>,..., D(n+x>) for the administration of the next or further dosage form(s) of the medicinal product (DFAMn, DFAM<n+i), DFAM(n+2> ,..., DFAM(n+x>) taking into account the read and recorded data; and wherein it is further programmed □ to change, such as overwrite or replace or supplement with a more up-to-date value, the value stored in the data memory (M) for a therapeutically effective minimum concentration of the drug in an effect compartment (cAMetr / MiN) and / or the value for a therapeutically effective minimum concentration of an active metabolite of the drug in an effect compartment (cAMBeff / MiN) during the course of treatment, and / or □ to change the value for a therapeutically acceptable maximum concentration of the drug in an effect compartment (cAMetf / MAx) and / or the value for a therapeutically acceptable maximum concentration of an active metabolite of the drug in an effect compartment (cAMBeff / MAx) during the course of treatment, for example to overwrite or replace or to supplement with a more up-to-date one; an output device, in particular an information output device (17), for outputting information at the determined time(s) (tA n , tA< n +i), tA(n+2>,..., tA(n+x>) and / or the determined dose (D n , D<n+1), D(n+2),..., D(n+x> ) concerning the next or further dosage form(s) of the medicinal product (DFAM), Hatchmore Labs GmbH or to dispense the next or further dosage form(s) of the medicinal product (DFAM).

2. System (100) according to claim 1, wherein the numerical value describing the proportion of the medicinal product (MP) from a given dosage form of the medicinal product (DFMP) that is absorbed by the body is or comprises the bioavailability of the medicinal product (MP) in the given dosage form of the medicinal product (DFMP); and / or wherein the numerical value describing how the drug (D) is distributed in the body is or indicates the volume of distribution of the drug (D); and / or wherein the numerical value describing how long it takes for the concentration of the drug (D) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM) is the time-to-peak concentration of the drug (tmax(D)); and / or wherein the numerical value describing how long it takes for the concentration of an active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma, to reach a maximum after administration of a dosage form of the drug (DFAM) is the "time-to-peak concentration" (tmax(AMB>)) of an active metabolite of the drug (AMB); and / or wherein the numerical value describing how quickly the concentration of the drug (AM) in a compartment of the body, such as the blood, and in particular the blood plasma, decreases per unit of time is the half-life of the drug (AM) in a compartment of the body, such as the blood, and in particular the blood plasma half-life; and / or where the numerical value describing how quickly the concentration of an active metabolite of the drug (AMB) decreases in a compartment of the body, such as the blood, and in particular the blood plasma, per unit of time is the half-life of the active metabolite of the drug (AMB) in a compartment of the body, such as the blood, and in particular the blood plasma half-life; and / or where the numerical value describing the amount of the drug (AM) eliminated from the body per unit of time is the clearance of the drug (AM); and / or where the numerical value describing the amount of an active metabolite of the drug (AMB) that is eliminated from the body per unit of time is the clearance of the active metabolite of the drug (AMB).

3. System (100) according to any one of the preceding claims, wherein the feedback device (8) is configured to record patient data relating to the time (tUAMW) of an insufficient drug response (UAMW) and / or the time (tzAMw) of a satisfactory drug response (ZAMW) in patients (P) and / or the time (tuMv) of an insufficient drug tolerability (UMV) and / or the time (tzMv) of a satisfactory drug tolerability (ZMV).

4. System (100) according to any one of the preceding claims, further showing a detection device (11) for detecting an administration pattern of the medicinal product (MP) to the patient (P), the administration pattern at least comprising Hatchmore Labs GmbH the time of administration (tA< n -i)) and the dose (D< n-1)) the most recently administered dosage form of the medicinal product (DFAM); wherein the electronic control device (9) is further programmed to evaluate or take into account the administration pattern detected by the detection device (11); and the determination of the time and / or dose of the next or further dosage form(s) of the medicinal product (DFAM) to be administered to the patient (P) is carried out taking into account the recorded administration pattern or the evaluation.

5. System (100) according to any of the preceding claims, wherein the electronic control device (9) is programmed, to store the data in memory (M) at time (tA< n -i)) the administration of the last dosage form of the medicinal product (DFAM( n-i>) to increase the existing value for the therapeutically effective minimum concentration (cAMeff / MiN(tA(ni))) if the time of onset of insufficient drug effect (tuAMw) is a time for which the calculation of the drug concentration (cAM) based on the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data store (M) is e ff(tuAMw) in the compartment, especially in the effects compartment, is greater than the value in the data storage (M) at time (tA< n -i)) the administration of the last dosage form (D< n -1)) of the drug (AM) present value for the therapeutic minimum concentration (cAMeff / MiN(tA(ni))), such that at time (tA n ) of the administration of the next dosage form of the drug (DFAMn) in the data store (M) a value for the therapeutically effective minimum concentration (cAMeff / MiN(tA)n )) is present, which is greater than the value for the minimum concentration (cAMeff / MiN(tA(ni))) when administering the last dosage form (DFAM< n -i)).

6. System (100) according to any one of the preceding claims, where determining the time of delivery (tA) is the calculation of the delivery time. n ) and / or the dose (D n ) the next dosage form of the drug to be administered to the patient (DFAMn).

7. System (100) according to any one of the preceding claims, wherein the electronic control device (9) is further programmed such that the determination of the time (tAn) and / or the dose (D) n) the next dosage form of the medicinal product (DFAMn) to be administered to a patient (P) is determined by relating the patient data recorded by the feedback device (8) at at least one specific time point, or for that time point, to a determination, in particular calculation, of the concentration of the medicinal product (cAM) and / or the active metabolite of the medicinal product (cAMB) in a compartment of the patient's body (P) for the same time point, carried out by the electronic control device (9) on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M), where determining the concentration of the drug (cAM) in a compartment and / or the concentration of the active metabolite of the drug (cAMB) in a compartment is or comprises a calculation of the concentration of the drug in a compartment (cAMeff) and / or the concentration of the active metabolite of the drug in a compartment (cAMBetf) performed on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M). Hatchmore Labs GmbH 8. System (100) according to claim 7, wherein the electronic control device (9) is programmed to read out pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data from the data storage (M), which show a time course of the concentration of the drug (cAM). eto map the time course of the drug concentration (cAM) in the patient's body (P) and then, based on this time course, to determine the concentration of the drug (cAM). e ff(t)) the time (tAnmax) and / or the magnitude of the next maximum concentration of the drug (cAM) e to calculate ff(tAnmax)) in the compartment, where patient data concerning inadequate drug response (ADR) are used in determining the time point (tA) n ) and / or the dose (D n ) the next dosage form of the drug to be administered to a patient (P) (DFAMn) is not taken into account if the time of its occurrence (tuAMw) is a time after the time (tA< n -i)) the administration of the last dosage form of the medicinal product (DFAM< n- i;), but before the time of the last maximum of the drug concentration (cAMeff(tA(ni)max)), and if, for that time, the drug concentration (cAMefr(tuAMw)) calculated on the basis of the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic data stored in the data storage (M) is less than the value of a predefined minimum effective concentration of the drug in the compartment, in particular less than the value of a predefined minimum therapeutically effective concentration of the drug (cAMetr / MiN) in the effect compartment.

9. System (100) according to any one of claims 6 to 8, wherein the electronic control device (9) is programmed to determine the next dosage form (DFAMn) to be administered to the patient (P) in such a way that the next maximum of the drug in the compartment (cAMeff(tAnmax)) will not exceed a predetermined therapeutic maximum (cAMetf / MAx) stored in the data memory (M) in the compartment, in particular in the effect compartment.

10. System (100) according to claim 9, wherein patient data relating to insufficient drug tolerance (UMV) are used to determine the time (tA) n ) and / or the dose (D n) the next dosage form of the drug (DFAMn) to be administered to a patient (P) is taken into account by reducing a therapeutic maximum (cAMetf / MAx) stored in the data store (M) so that at the time of administration of the next dosage form (tAn) of the drug (DFAMn) a value for the therapeutic maximum concentration (cAM) is stored in the data store (M). e ff / MAx(tA n )) is present, which is smaller than the therapeutically effective maximum concentration (cAMeff / MAx(tA(ni))) for the administration of the last dosage form (DFAM< n -i)).

11. System (100) according to any one of claims 6 to 10, wherein the electronic control device (9) is programmed to read out pharmacological, pharmacodynamic, pharmacogenetic, pharmacometric and / or pharmacokinetic data from the data storage (M) which represent a time course of the concentration of the drug (cAM(t)) in the body of the patient (P), and then, based on these, to adjust the concentration (cAM(tA nmax + tx )) to one maximum after the next (cAM e ff(tAnmax)) of the concentration at a given time (tA nmax + tx ) in a compartment, especially in the effect compartment, and is further programmed to, when the dose (D n ) the next dosage form to be administered (DFAMn) is specified, when determining its time (tAn) of administration to the patient (P), taking into account in the data storage (M) Hatchmore Labs GmbH stored data and a therapeutic minimum concentration (cAMetr / MiN) held in the data storage (M), the time (tA n ) such that the concentration (cAM(tA) n )) after a final maximum of the concentration (cAM(tA(ni)max) does not fall below the value for the specified therapeutically effective minimum concentration (cAMetr / MiN) in the compartment, especially in the effect compartment.

12. System (100) according to one of the preceding embodiments, wherein the output device is used as an information output device (17) to output information at the determined time (tA) n ) and / or the determined dose (Dn) of the next dosage form of the medicinal product (DFAM) relating to the information is displayed visually or audibly on a device or is configured to do so or is prepared to transmit a signal to a device for this purpose.

13. System (100) according to any one of the preceding claims, wherein the feedback device (8), or some or all functional components of the feedback device (8), on the one hand, and the output device (17) on the other hand, are part of the same device or apparatus.

14. System (100) according to any one of the preceding claims, wherein the electronic control device (9), or some or all of the functional components of the electronic control device (9), on the one hand, and the data storage device (M) on the other hand, are part of the same device or apparatus.

15. System (100) according to any one of the preceding claims, wherein the electronic control device (9), or some or all functional components of the electronic control device (9), on the one hand, and the detection device (11), on the other hand, are part of the same device or apparatus.

16. System (100) according to any one of the preceding claims, wherein the output device (17), or some or all functional components of the output device (17), on the one hand, and the detection device (8) on the other hand, are part of the same device or apparatus.

17. System (100) according to any one of the preceding claims, wherein the feedback device (8), or some or all of the functional components of the feedback device (8), on the one hand, and the detection device (11) on the other hand, are part of the same device or apparatus.

18. System (100) according to claim 17, wherein the output device (17), the detection device (11) and the feedback device (8), and / or their functional components, are part of the same device or apparatus.

19. System (100) according to any one of the preceding claims, further showing a dosage form of the drug (DFAM).

20. A medicinal product for use or application in the treatment of a disease, wherein the timing and / or dose of the next Hatchmore Labs GmbH treatment is to be administered to a patient The dosage form of the drug is determined by an electronic control device by a feedback device (8) records patient data concerning the patient's response to the last administration of a dosage form of the medicinal product (DFAM); the electronic control device reads from a data storage device data concerning administration times (tAo, tAi, tA2, tA(ni>) of one or more previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2, DFAM(ni)) and / or concerning the dose (Do, Di, D2,..., D(n-1>) of these previously administered dosage forms of the medicinal product (DFAMo, DFAMi, DFAM2,..., DFAM(ni)); the electronic control device reads pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP) from a data storage device (M); wherein the feedback device (8) is configured to record patient data relating to the time (tUAMW) of an insufficient drug response (UAMW) and / or the time (tzAMw) of a satisfactory drug response (ZAMW) in patients (P) and / or the time (tuMv) of an insufficient drug tolerability (UMV) and / or the time (tzMv) of a satisfactory drug tolerability (ZMV); and wherein the electronic control device is further programmed to change, for example overwrite or replace or supplement with a more up-to-date value, the value stored in the data store (M) for a therapeutically effective minimum concentration of the drug in an effect compartment (cAMeff / MiN) and / or the value for a therapeutically effective minimum concentration of an active metabolite of the drug in an effect compartment (cAMBetr / MiN) during the course of treatment, and / or to change the value for a therapeutically acceptable maximum concentration of the drug in an effect compartment (cAMeff / MAx) and / or the value for a therapeutically acceptable maximum concentration of an active metabolite of the drug in an effect compartment (cAMBetf / MAx) during the course of treatment, for example to overwrite or replace it or to supplement it with a more up-to-date one; and wherein the electronic control device takes into account the patient data relating to the patient's response to the last administration, the data relating to the administration times and / or the last dose, and the data relating to the pharmacological, pharmacodynamic, pharmacometric, pharmacogenetic and / or pharmacokinetic models relating to the medicinal product (MP) when determining the next time and / or the next dose of the dosage form to be administered to a patient.

21. The medicament for use in the treatment of a disease according to claim 20, wherein the medicament is a drug from ATC class N and the disease is a disease of the nervous system.

22. The medicament for use according to claim 21, wherein the medicament is of ATC class N06A or N05A, for the treatment of depression and / or schizophrenia.

23. The medicament for use in the treatment of a disease according to claim 20, wherein the medicament interacts with a drug target and the drug target is a receptor.

24. The medicament for use according to claim 23, wherein the medicament is ketamine, R-ketamine or S-ketamine and the drug target is Q05586, Q12879, Q13224, Q14957 and / or 015399. Hatchmore Labs GmbH 25. The medicament for use according to claim 23, wherein the medicament comprises a dichlorophenyl piperazine group and the drug target is P35462 and / or P14416 and / or P08908 and / or P28223 and / or P41595.

26. The medicament for use according to claim 25, wherein the medicament is cariprazine, aripiprazole or brexpiprazole.

Images