Mechanistic Static Model based Prediction of Transporter Substrate Drug-Drug Interactions Utilizing Atorvastatin and Rifampicin.

Objective: An in vitro relative activity factor (RAF) technique combined with mechanistic static modeling was examined to predict drug-drug interaction (DDI) magnitude and analyze contributions of different clearance pathways in complex DDIs involving transporter substrates. Atorvastatin and rifampicin were used as a model substrate and inhibitor pair.

Methods: In vitro studies were conducted with transfected HEK293 cells, hepatocytes and human liver microsomes.