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Expert Opin Drug Metab Toxicol. 2009 May;5(5):489-500. doi: 10.1517/17425250902911463 .

In vitro evidence for the role of OATP and OCT uptake transporters in drug-drug interactions.

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1
Friedrich-Alexander-University Erlangen-Nuremberg, Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology and Clinical Toxicology, Fahrstrasse 17, D-91054 Erlangen, Germany.

Abstract

BACKGROUND:

Transport proteins, for example the drug export pump P-glycoprotein, are important for the absorption, distribution and excretion of drugs. Inhibition and induction of P-glycoprotein efflux function is a well-established mechanism of drug-drug interactions. Alteration of transporter-mediated drug uptake by concomitantly administered drugs may also result in a change in drug pharmacokinetics. These uptake transporter-mediated drug-drug interactions are the focus of this review.

OBJECTIVE:

To examine the current in vitro evidence on interactions mediated by OATPs (organic anion transporting polypeptides) and OCTs (organic cation transporters).

METHODS:

Comparing data of in vivo observed drug-drug interactions with in vitro analysed alterations in drug transport mediated by the hepatic expressed uptake transporters OATP1B1, OATP1B3 and OCT1 and by the renal expressed OCT2 protein.

RESULTS/CONCLUSIONS:

Some of the previously in vivo described drug-drug interactions could be explained by alteration in uptake transporter function demonstrating that inhibition or induction of uptake transporters is a newly recognised mechanism of potential drug-drug interactions.

PMID:
19416085
DOI:
10.1517/17425250902911463
[Indexed for MEDLINE]
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