Clinical Drug Investigation

, Volume 21, Issue 8, pp 587–596 | Cite as

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

Focus on H1-Receptor Antagonists
  • Philip D. Hansten
  • Rene H. Levy
Review Article


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.


Digoxin Terfenadine Loratadine Grapefruit Juice Fexofenadine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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


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Copyright information

© Adis International Limited 2001

Authors and Affiliations

  1. 1.Department of PharmacyUniversity of Washington School of PharmacySeattleUSA
  2. 2.Department of PharmaceuticsUniversity of Washington School of PharmacySeattleUSA

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