Physiologically-Based Pharmacokinetic Modeling Analysis for Quantitative Prediction of Renal Transporter-Mediated Interactions Between Metformin and Cimetidine.

ABSTRACT: Metformin is an important antidiabetic drug and often used as a probe for drug-drug interactions (DDIs) mediated by renal transporters. Despite evidence supporting the inhibition of multidrug and toxin extrusion proteins as the likely DDI mechanism, the previously reported physiologically-based pharmacokinetic (PBPK) model required the substantial lowering of the inhibition constant values of cimetidine for multidrug and toxin extrusion proteins from those obtained in vitro to capture the clinical DDI data between metformin and cimetidine.1 We constructed new PBPK models in which the transporter-mediated uptake of metformin is driven by a constant membrane potential. Our models successfully captured the clinical DDI data using in vitro inhibition constant values and supported the inhibitio

SUBMITTER: Nishiyama K 

PROVIDER: S-EPMC6617824 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature