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Role of P-Glycoprotein and Organic Anion Transporting Polypeptides in Drug Absorption and Distribution

Focus on H1-Receptor Antagonists

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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 Hi-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.

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Acknowledgements

This publication was funded, in part, by an educational grant from the Schering-Plough Research Institute.

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Authors and Affiliations

  1. Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, Washington, WA 98195-7630, USA

    Philip D. Hansten

  2. Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA

    Rene H. Levy

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Correspondence to Philip D. Hansten.

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Hansten, P.D., Levy, R.H. Role of P-Glycoprotein and Organic Anion Transporting Polypeptides in Drug Absorption and Distribution. Clin. Drug Investig. 21, 587–596 (2001). https://doi.org/10.2165/00044011-200121080-00008

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