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Review

Transporter-Mediated Drug–Drug Interactions

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Pages 1017-1037 | Published online: 25 Jul 2011
 

Abstract

Drug–drug interactions are a serious clinical issue. An important mechanism underlying drug–drug interactions is induction or inhibition of drug transporters that mediate the cellular uptake and efflux of xenobiotics. Especially drug transporters of the small intestine, liver and kidney are major determinants of the pharmacokinetic profile of drugs. Transporter-mediated drug–drug interactions in these three organs can considerably influence the pharmacokinetics and clinical effects of drugs. In this article, we focus on probe drugs lacking significant metabolism to highlight mechanisms of interactions of selected intestinal, hepatic and renal drug transporters (e.g., organic anion transporting polypeptide [OATP] 1A2, OATP2B1, OATP1B1, OATP1B3, P-gp, organic anion transporter [OAT] 1, OAT3, breast cancer resistance protein [BCRP], organic cation transporter [OCT] 2 and multidrug and toxin extrusion protein [MATE] 1). Genotype-dependent drug–drug interactions are also discussed.

Financial & competing interests disclosure

The authors‘ work is supported by the German Cancer Aid (Deutsche Krebshilfe, #107854), the DFG (Deutsche Forschungsgemeinschaft FR1298/5–1) and the DOKTOR ROBERT PFLEGER-STIFTUNG Bamberg. Martin F Fromm received consulting fees from AstraZeneca, Bayer Schering Pharma, Boehringer Ingelheim and Merck KGaA and lecture fees from Bayer Schering Pharma, Ferring and Novartis. Fabian Müller owns minor stock in Novartis and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors‘ work is supported by the German Cancer Aid (Deutsche Krebshilfe, #107854), the DFG (Deutsche Forschungsgemeinschaft FR1298/5–1) and the DOKTOR ROBERT PFLEGER-STIFTUNG Bamberg. Martin F Fromm received consulting fees from AstraZeneca, Bayer Schering Pharma, Boehringer Ingelheim and Merck KGaA and lecture fees from Bayer Schering Pharma, Ferring and Novartis. Fabian Müller owns minor stock in Novartis and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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