Drug Safety

, Volume 28, Issue 9, pp 789–801 | Cite as

The Role of P-Glycoprotein and Organic Anion-Transporting Polypeptides in Drug Interactions

  • Lawrence M. DuBuskeEmail author
Review Article


The use of polytherapy in clinical practice necessitates an appreciation and understanding of the potential for drug interactions. Recent publications provide insight into the role of the active transport systems P-glycoprotein (P-gp) and human organic anion-transporting polypeptides (OATPs) in drug interactions. Active drug transporters influence the bioavailability of a number of drugs by controlling their movement into, and out of, cells.

The active transport systems P-gp and OATP play an important role in drug elimination. The activity of these transport systems is controlled, in part, by genetic factors; however, drugs and foods also influence the activity of these systems. It appears that interference with P-gp or OATP, either as upregulation or inhibition, may affect plasma drug concentrations by altering intestinal absorption, proximal renal-tubular excretion or biliary excretion. Overall, the net bioavailability of a drug or substance is affected by the relative contributions of cellular efflux (P-gp) and influx (OATP) mechanisms and to what extent these systems are active during phases of uptake and absorption versus removal and excretion from the body.

Many of the drugs and foods that affect active drug transport activity are known to interact with the cytochrome P450 enzyme system; therefore, the net effect of concomitant drug administration is complex. One must now consider the impact of metabolism (CYP-mediated drug biotransformation), P-gp-mediated drug efflux and OATP-mediated uptake when making assessments of drug absorption and distribution.


Digoxin Ketoconazole Terfenadine 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.



Prepared with editorial assistance from Charles Miller, Apothecom and Hannah Ridgway, Gardiner-Caldwell Thomson, with financial assistance from Schering-Plough. Dr DuBuske has received research grants from Genentech, GlaxoSmithKline, Merck, Novartis and Schering-Plough. He has received consulting fees or other renumeration (payment) from Allergy Therapeutics, Altana, Genentech, MedPointe, Merck, Novartis and Schering-Plough and is also a member of their speakers’ bureaus.


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© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Immunology Research Institute of New EnglandGardnerUSA

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