Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interaction Potential of Vemurafenib Using R-Value and Physiologically-Based Pharmacokinetic Models.

ABSTRACT: Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important determinants of transporter-mediated drug-drug interactions (DDIs). Current studies assessed the OATP1B1 and OATP1B3-mediated DDI potential of vemurafenib, a kinase inhibitor drug with high protein binding and low aqueous solubility, using R-value and physiologically-based pharmacokinetic (PBPK) models. The total half-maximal inhibitory concentration (IC_50,total) values of vemurafenib against OATP1B1 and OATP1B3 were determined in 100% human plasma in transporter-overexpressing human embryonic kidney 293 stable cell lines. The unbound fraction of vemurafenib in human plasma before (f_u,plasma) and after addition into the uptake assay plate (f_u,plasma,inc) were determined by rapid eq

SUBMITTER: Kayesh R 

PROVIDER: S-EPMC7750294 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature