A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Drug-Drug-Gene Interaction Model of Metformin and Cimetidine in Healthy Adults and Renally Impaired Individuals.

ABSTRACT:

Background

Metformin is a widely prescribed antidiabetic BCS Class III drug (low permeability) that depends on active transport for its absorption and disposition. It is recommended by the US Food and Drug Administration as a clinical substrate of organic cation transporter 2/multidrug and toxin extrusion protein for drug-drug interaction studies. Cimetidine is a potent organic cation transporter 2/multidrug and toxin extrusion protein inhibitor.

Objective

The objective of this study was to provide mechanistic whole-body physiologically based pharmacokinetic models of metformin and cimetidine, built and evaluated to describe the metformin-SLC22A2 808G>T drug-gene interaction, the cimetidine-metformin drug-drug interaction, and the impact of renal impairment on metformin expo

SUBMITTER: Hanke N 

PROVIDER: S-EPMC7658088 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature