Physiologically Based Pharmacokinetic Modeling of Rosuvastatin and Prediction of Transporter-Mediated Drug-Drug Interactions Involving Rifampicin

Conference: BioMed
Software: GastroPlus®
Division: PBPK


Statins have been extensively used worldwide for the treatment of cardiovascular diseases. However, compliance which is a key for the best treatment outcomes is the issue due to the side effects. Understanding the underlying mechanisms involved in the disposition of statins is required for optimal dosing to improve compliance. PBPK modeling approach allows to investigate and identify the underlying mechanisms to better understand ADME processes and determinants of drug interactions. Rosuvastatin (Crestor®) is a commonly prescribed lipid-lowering agent from the statins class for the treatment of primary hyperlipidemia and hypertriglyceridemia. Rosuvastatin is a substrate for multiple transporters including organic anion transporting polypeptides (OATP1B1 and OATP1B3), sodiumtaurocholate cotransporting polypeptide (NTCP), breast cancer resistance protein (BCRP), and exhibits minor metabolic clearance. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model of rosuvastatin and to apply this model to predict the transporter-mediated drug-drug interactions (DDIs) with rifampicin, which is an inhibitor of multiple drug transporters

Bu Joyce Macwan, Viera Lukacova, Grace Fraczkiewicz

BioMedical Transporters in Lucerne, Switzerland  August 4-8, 2019