Hepatic and intestinal drug transporters: prediction of pharmacokinetic effects caused by drug-drug interactions and genetic polymorphisms

Annu Rev Pharmacol Toxicol. 2013;53:581-612. doi: 10.1146/annurev-pharmtox-011112-140309. Epub 2012 Nov 8.


Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altered; this alteration influences the substrate drugs' subsequent pharmacological or toxicological effects. In predicting these effects quantitatively from in vitro experimental results, we must first determine the contribution of each transporter to the overall elimination process. Furthermore, the accurate estimation of effective inhibitor concentrations at the site of interaction (e.g., intestinal lumen, extracellular and intracellular space of hepatocytes) is challenging. In predicting pharmacogenetic effects, the extrapolation from in vitro observations to in vivo outcomes (e.g., changes in intrinsic activities and/or expression levels) is still evolving. In this review, we describe the current status of, and difficulties inherent in, the accurate prediction of the altered pharmacokinetics caused by transporter-mediated DDIs and pharmacogenetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Drug Interactions*
  • Humans
  • Intestinal Mucosa / metabolism*
  • Liver / metabolism*
  • Pharmacokinetics*
  • Polymorphism, Genetic*