An Updated In Silico Prediction Method for Volumes of Systemic Circulation of 323 Disparate Chemicals for Use in Physiologically Based Pharmacokinetic Models to Estimate Plasma and Tissue Concentrations after Oral Doses in Rats

Updated algorithms for predicting the volumes of systemic circulation (V-1), along with absorption rate constants and hepatic intrinsic clearances, as input parameters for physiologically based pharmacokinetic (PBPK) models were established to improve the accuracy of estimated plasma and tissue concentrations of 323 chemicals after virtual oral administrations in rats. Using ridge regression with an enlarged set of chemical descriptors (up to 99), the estimated input V-1 values resulted in an improved correlation coefficient (from 246 compounds) with the traditionally determined values. The PBPK model input parameters for rats of diverse compounds can be precisely estimated by increasing the number of descriptors.