Toward Prospective Prediction of Pharmacokinetics in OATP1B1 Genetic Variant Populations.

ABSTRACT: Physiologically based pharmacokinetic (PBPK) models are increasingly being used to provide human pharmacokinetic (PK) predictions for organic anion-transporting polypeptide (OATP) substrates based on in vitro assay data. As a natural extension in the application of these models, in this study, we incorporated in vitro information of three major OATP1B1 genetic variants into a previously reported PBPK model to predict the impact of OATP1B1 polymorphisms on human PK. Using pravastatin and rosuvastatin as examples, we showed that the predicted plasma concentration-time profiles in groups carrying different OATP1B1 genetic variants reasonably matched the clinical observations from multiple studies. This modeling and simulation approach may aid decision making in early pharmaceutical research a

SUBMITTER: Li R 

PROVIDER: S-EPMC4288003 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature