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.