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Introduction. Deferasirox is a complexing drug and belongs to class II according to the biopharmaceutical classification system (BCS), has acidic properties and belongs to subclass “a” (acid). This class is characterized by high permeability and low solubility, which limits the absorption of the active substance into the blood. As a result, the development of drugs with an active substance that can be assigning BCS to this class is a difficult task, and for generic drugs it is also associated with a high risk of obtaining unproven equivalence during clinical trials. To minimize the above risks, a physiologically relevant test was carried out with further data processing and construction of putative pharmacokinetic profiles.Aim. The aim of the study is to conduct a physiologically relevant test (PRT) to predict in vitro pharmacokinetic profiles and compare them with in vivo data as part of a bioequivalence study of deferasirox.Materials and methods. The objects of the study are "Deferasirox, film-coated tablets, 360 mg" of a domestic manufacturer and "Jadenu®, film-coated tablets, 360 mg" (WTN22 series, expiration date until 10.2023, Novartis Pharma Stein AG, Switzerland). A physiologically relevant test was performed on the device SC PRT-6, Compliance. Quantitative analysis was carried out by HPLC-UV method.Pharmacokinetic profiles were modeled using PK-Sim® (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany) based on data obtained from physiologically relevant test.Results and discussion. A physiologically relevant drug test for deferasirox was performed and release profiles were obtained, which formed the basis of a physiologically based pharmacokinetic model together with data on the physicochemical properties of the studied compound and literature data on the pharmacokinetics of deferasirox. The pharmacokinetic profiles obtained as part of the simulation on a virtual population were compared with data obtained during clinical trials.Conclusion. A physiologically relevant test for the drug deferasirox was carried out, quantitative determination in the samples was carried out by HPLC-UV. The test resulted in data that allowed prediction of pharmacokinetic profiles that reflected the same differences observed in the profiles of the test and reference drug in the comparative pharmacokinetics and bioequivalence study of deferasirox drugs.

Introduction. Sorafenib is an antineoplastic drug belonging to class IIc according to the biopharmaceutical classification system (BCS) due to the presence of both acidic and basic properties. In addition to low solubility, sorafenib is characterized by high variability during clinical trials, in particular bioequivalence studies (BE). To selecting batches that can be recommended for BE studies, the dissolution kinetics test is currently widely used, however, the results of this test are not always sufficient and additional tests, for example, a physiologically relevant test, are advisable. To minimize the risks of obtaining nonequivalent results during the BE study, a physiologically relevant test (PRT) was carried out with further data processing and interpretation of the results of physiologically based pharmacokinetic modeling (PBPK).Aim. The aim of the study is to conduct a physiologically relevant test (PRT) for the purpose of selecting a candidate batch for subsequent BE study of sorafenib drugs using the physiologically based pharmacokinetic model (PBPK).Materials and methods. The objects of the study are Nexavar®, film-coated tablets, 200 mg (Bayer AG, Germany) (one batch) and Sorafenib, film-coated tablets, 200 mg (two batches) (Russia). The physiologically relevant test was performed on the SC PRT-6 device (LLC "Scientific Compliance", Russia). Quantitative analysis was performed by HPLC-UV on the Chromatec-Crystal HPLC 2014 device (CJSC "Chromatec", Russia). The plasma concentration profiles were simulated using PK-Sim® software (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany).Results and discussion. As part of the study, a method for the quantitative determination of sorafenib was developed and validated, a method for sample preparation was developed, and a method for conducting the PRT for sorafenib, as a representative of the IIc subclass of BCS, was developed. Based on the study results, release profiles were obtained that were used to select a candidate series for the BE study. The series were selected based on the PBPK analysis on a virtual population consisting of 36 healthy volunteers with activated enteropathic circulation, characteristic of sorafenib.Conclusion. The PRT was carried out for the drug sorafenib. Quantitative determination was carried out by HPLC-UV according to the developed and validated method. The test resulted in obtaining data that were subjected to PBPK analysis. It was shown that the studied batches have high risks of non-equivalence during the bioequivalence study.