Predictive Performance of Next Generation Physiologically Based Kinetic (PBK) Model Predictions in Rats Based on In Vitro and In Silico Input Data.

ABSTRACT: The goal of the present study was to assess the predictive performance of a minimal generic rat physiologically based kinetic (PBK) model based on in vitro and in silico input data to predict peak plasma concentrations (Cmax) upon single oral dosing. To this purpose, a dataset was generated of 3960 Cmax predictions for 44 compounds, applying different combinations of in vitro and in silico approaches for chemical parameterization, and comparison of the predictions to reported in vivo data. Best performance was obtained when (1) the hepatic clearance was parameterized based on in vitro measured intrinsic clearance values, (2) the method of Rodgers and Rowland for calculating partition coefficients, and (3) in silico calculated fraction unbound plasma and Papp values (the latter especially f

SUBMITTER: Punt A 

PROVIDER: S-EPMC8883350 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature