High-throughput in-silico prediction of ionization equilibria for pharmacokinetic modeling.

ABSTRACT: Chemical ionization plays an important role in many aspects of pharmacokinetic (PK) processes such as protein binding, tissue partitioning, and apparent volume of distribution at steady state (Vd_ss). Here, estimates of ionization equilibrium constants (i.e., pK_a) were analyzed for 8132 pharmaceuticals and 24,281 other compounds to which humans might be exposed in the environment. Results revealed broad differences in the ionization of pharmaceutical chemicals and chemicals with either near-field (in the home) or far-field sources. The utility of these high-throughput ionization predictions was evaluated via a case-study of predicted PK Vd_ss for 22 compounds monitored in the blood and serum of the U.S. population by the U.S. Centers for Disease Control and P

SUBMITTER: Strope CL 

PROVIDER: S-EPMC6055917 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature