Modeled Rat Hepatic and Plasma Concentrations of Chemicals after Virtual Administrations Using Two Sets of in Silico Liver-to-Plasma Partition Coefficients.

The hepatic elimination of chemical substances in pharmacokinetic models requires hepatic intrinsic clearance (CL) parameters for unbound drug in the liver, and these are regulated by the liver-to-plasma partition coefficients (K). Both Poulin and Theil and Rodgers and Rowland have proposed in silico expressions for K for a variety of chemicals. In this study, two sets of in silico K values for 14 model substances were assessed using experimentally reported in vivo steady-state K data and time-dependent virtual internal exposures in the liver and plasma modeled by forward dosimetry in rats.