Application of Physiologically Based Pharmacokinetic Modeling in Preclinical Studies: A Feasible Strategy to Practice the Principles of 3Rs.

ABSTRACT: Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the in vivo profiles of drug absorption, distribution, metabolism, and excretion can be predicted. To evaluate the application of such an approach in preclinical investigations, the plasma pharmacokinetic profiles of seven commonly used probe substrates of microsomal enzymes, including phenacetin, tolbutamide, omeprazole, metoprolol, chlorzoxazone, nifedipine, and baicalein, were predicted in rats using bottom-up PBPK models built with in vitro data

SUBMITTER: Yuan Y 

PROVIDER: S-EPMC9133488 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature