Using Physiologically Based Pharmacokinetic Modeling for in vitro – in vivo Extrapolation to Predict Chemical Exposure

Division: Simulations Plus


Mechanistic absorption and physiologically based pharmacokinetic (MA/ PBPK) models are useful tools in risk assessment. These models incorporate complex processes related to a compound’s disposition, such as dissolution, absorption, metabolism, and protein binding in plasma and tissues, and also offer the possibility of predicting target tissue concentrations. In this study, the MA/PBPK model in GastroPlus™ version 9.0 was applied to predict the exposure of eighteen chemicals with reported exposure in human after oral administration. The in vivo metabolism was estimated from either in vitro metabolic clearance measured in human hepatocytes (Wetmore et al. Toxicol Sci, 125(2012) and 148(2015)) or in silico predictions (ADMET Predictor™ version 7.2) .

PBPK IVIVE to Predict Chemical Exposure IVIVE Workshop 2016

By Haiying Zhou, Grazyna Fraczkiewicz, Michael Lawless