An Updated <i>In Silico</i> 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
(V1), 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 V1 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.