Prediction of Hepatic Efflux Transporter-Mediated Drug Interactions: When Is it Optimal to Measure Intracellular Unbound Fraction of Inhibitors?

ABSTRACT: The intracellular unbound inhibitor concentration ([I]_unbound,cell) is the most relevant concentration for predicting the inhibition of hepatic efflux transporters. However, the intracellular unbound fraction of inhibitor in hepatocytes (f_{u,cell,inhibitor}) is not routinely determined. Studies are needed to evaluate the benefit of measuring f_{u,cell,inhibitor} and using [I]_unbound,cell versus intracellular total inhibitor concentration ([I]_total,cell) when predicting inhibitory effects. This study examined the benefit of using [I]_unbound,cell to predict hepatocellular bile acid disposition. Cellular total concentrations of taurocholate ([TCA]_total,cell), a prototypical bile acid, were simulated using pharmacokinetic

SUBMITTER: Guo C 

PROVIDER: S-EPMC5617730 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature