ORIGINAL RESEARCH ARTICLE A Mechanistic Framework for In Vitro–In Vivo Extrapolation of Liver Membrane Transporters: Prediction of Drug–Drug Interaction Between Rosuvastatin and Cyclosporine

The Author(s) 2013. This article is published with open access at Springerlink.com Background and Objectives The interplay between liver metabolising enzymes and transporters is a complex process involving system-related parameters such as liver blood per-fusion as well as drug attributes including protein and lipid binding, ionisation, relative magnitude of passive and active permeation. Metabolism- and/or transporter-mediated drug– drug interactions (mDDIs and tDDIs) add to the complexity of this interplay. Thus, gaining meaningful insight into the impact of each element on the disposition of a drug and accurately predicting drug–drug interactions becomes very challenging. To address this, an in vitro–in vivo extrapolation (IVIVE)-linked mechanistic physiologically based pharma-cokinetic (PBPK) framework for modelling liver transporter