Transporter-mediated drug-drug interactions. Pharmacogenomics

Institute of Experimental & Clinical Pharmacology & Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054 Erlangen, Germany.
Pharmacogenomics (Impact Factor: 3.43). 07/2011; 12(7):1017-37. DOI: 10.2217/pgs.11.44
Source: PubMed

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.

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    • "Induction of P-gp can provoke elimination of P-gp substrates and decrease their bioavailability. In contrast, inhibition can increase bioavailability and amplify therapeutic efficacy, but also toxicity [3] [9]. An example of inhibition is the interaction of loperamide and P-gp inhibitors at the blood–brain barrier. "
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    Biochemical Pharmacology 01/2015; 94(3). DOI:10.1016/j.bcp.2015.01.008 · 4.65 Impact Factor
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    • "The involvement of cytochrome P450 (CYP), phase II metabolic enzymes and transport proteins in pharmaco-kinetic DDI has been detailed in various publications (Shitara et al., 2003; Müller and Fromm, 2011). The major isoforms of CYP involved in drug metabolism are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. "
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