Predicting the Pharmacokinetics of Orally Administered Drugs across BCS Classes 1–4 by Virtual Bioequivalence Model

Abstract

To evaluate the influence of solubility and permeability on the pharmacokinetic prediction performance of orally administered drugs using avirtual bioequivalence (VBE) model, a total of 23 orally administered drugs covering Biopharmaceutics Classification System (BCS) classes 1−4 were selected. A VBE model (i.e., a physiologically based pharmacokinetic model integrated with dissolution data) based on a B 2 O simulator was applied for pharmacokinetic (PK) prediction in a virtual population. Parameter sensitivity analysis was used for input parameter selection. The predictive performances of PK parameters (i.e., AUC 0−t , C max , and T max ), PK profiles, and bioequivalence (BE) results were evaluated using the twofold error, average fold error (AFE), absolute average fold error (AAFE), and BE reassessment metrics. All models successfully simulated the mean PK profiles, with AAFE < 2 and AFE ranging from 0.58 to 1.66. As for the PK parameters, except for the time of peak concentration, T max , of isosorbide mononitrate, other simulated PK parameters were all within a twofold error. The simulated PK behaviors were comparable to the observed ones, both for test (T) and reference (R) products, and the simulated T/R arithmetic mean ratios were all within 0.88−1.16 of the observed values. These four evaluation metrics were distributed equally among BCS class 1−4 drugs. The VBE model showed powerful performance to predict the PK behavior of orally administered drugs with various combinations of solubility and permeability, irrespective of the BCS category.

Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling

“…In this study, a PBPK model of IB inhalation aerosol was established in the B 2 O simulator (version 3.0, Shanghai Yinghan Pharmaceutical Technology Co., Ltd) to study the virtual bioequivalence of the test and reference products. The same simulator has already been used in bioequivalence studies (16)(17)(18), such as the study reported by Wu et al 2022, the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal spray was predicted using the nasal physiologically based pharmacokinetic (PBPK) model. The semi-PBPK model successfully depicted the absorption and distribution of intranasal varenicline in the respiratory tissues (17).…”