Role of P-Glycoprotein and Organic Anion Transporting Polypeptides in Drug Absorption and Distribution: Focus on H-Receptor Antagonists

Authors: Hansten P.D.¹; Levy R.H.²

Source: Clinical Drug Investigation, Volume 21, Number 8, 1 August 2001 , pp. 587-596(10)

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Abstract:

Traditionally, drug-induced changes in cytochrome P450 isoenzyme activity, causing changes in drug metabolism and bioavailability, have been the main focus of drug interaction studies. Recent research, however, suggests that the drug transporters P-glycoprotein and organic anion transporting peptide (OATP), which can effect the efflux and influx of many classes of drugs, may contribute to drug interactions by mechanisms independent of oxidative metabolism. Experimental models designed to selectively probe the function of P-glycoprotein or OATP have demonstrated that changes in the activities of these transporters may have a significant effect on the bioavailability of clinically important drugs, leading to the potential for adverse drug interactions.

This review focuses on what is known about the P-glycoprotein and OATP drug transporters and their effects on drug bioavailability. Where possible, it uses as examples the second-generation H-receptor antagonists, where concomitant administration of other drugs or food constituents has been shown to alter the bioavailability of some agents of this class via mechanisms probably mediated by P-glycoprotein and/or OATP.

Keywords: Antiallergics, pharmacokinetics; Antihistamines, pharmacokinetics; Histamine H1 receptor antagonists, pharmacokinetic

Document Type: Review article

Affiliations: 1: Department of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, USA 2: Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA

Publication date: 2001-08-01