Prediction of drug-drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling.

ABSTRACT:

Purpose

Recent in vitro studies demonstrated that dasatinib inhibits organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), and organic anion transporting polypeptide 1B1/1B3 (OATP1B1/1B3). We developed a physiologically based pharmacokinetic (PBPK) model to assess drug-drug interaction (DDI) potential between dasatinib and known substrates for these transporters in a virtual population.

Methods

The dasatinib PBPK model was constructed using Simcyp^® Simulator by combining its physicochemical properties, in vitro data, in silico predictions, and pharmacokinetic (PK) results from clinical studies. Model validation against three independent clinical trials not used for model development included dasatinib DDI studies with ketoconazole, r

SUBMITTER: Chang M 

PROVIDER: S-EPMC8882081 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature