Prediction of renal transporter-mediated drug-drug interactions for a drug which is an OAT substrate and inhibitor using PBPK modelling.

A PBPK modelling approach was used to predict organic anion transporter (OAT) mediated drug-drug interactions involving S44121, a substrate and an inhibitor of OAT1 and OAT3. Model predictions were then compared to the results of a clinical DDI study which was carried out to investigate the interaction of S44121 with probenecid, tenofovir and ciprofloxacin. PBPK models were developed and qualified using existing clinical data, and inhibition constants were determined in vitro.