Transporters and drug-drug interactions: important determinants of drug disposition and effects

König J, Fromm M, Müller F (2013)


Publication Type: Journal article, Review article

Publication year: 2013

Journal

Original Authors: König J, Müller F, Fromm MF

Publisher: American Society for Pharmacology and Experimental Therapeutics (ASPET)

Book Volume: 65

Pages Range: 944-966

Journal Issue: 3

DOI: 10.1124/pr.113.007518

Abstract

Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics. Available data on the impact of nutrition on transport processes as well as genotype-dependent, transporter-mediated drug-drug interactions will be discussed. We will also present and discuss data on the variable extent to which information on the impact of transporters on drug disposition is included in summaries of product characteristics of selected countries (SPCs). Further work is required regarding a better understanding of the role of the drug metabolism-drug transport interplay for drug-drug interactions and on the extrapolation of in vitro findings to the in vivo (human) situation.

Authors with CRIS profile

How to cite

APA:

König, J., Fromm, M., & Müller, F. (2013). Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacological reviews, 65(3), 944-966. https://doi.org/10.1124/pr.113.007518

MLA:

König, Jörg, Martin Fromm, and Fabian Müller. "Transporters and drug-drug interactions: important determinants of drug disposition and effects." Pharmacological reviews 65.3 (2013): 944-966.

BibTeX: Download