生物等效性
药代动力学
生物制药分类系统
最大值
药理学
数学
化学
医学
作者
Fan Zhang,Xiaofei Wu,Keheng Wu,Mengyang Yu,Bo Liu,Hongyun Wang
标识
DOI:10.1021/acs.molpharmaceut.2c00688
摘要
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 B2O 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., AUC0–t, Cmax, and Tmax), 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, Tmax, 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.
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