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Renal Drug Transport and Drug-Drug Interactions

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto

Reina Bendayan, PharmD

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, r.bendayan{at}utoronto.ca

The kidney plays a vital role in the elimination of xenobiotics including drugs, toxins, and endogenous metabolites. Renal drug elimination involves 3 major processes: glomerular filtration, tubular secretion, and tubular reabsorption. Although glomerular filtration is a simple unidirectional diffusion process, renal tubular secretion and/or reabsorption can involve saturable processes mediated by multiple highly specialized membrane transport systems. Current research has identified that these transport proteins play a significant role in the efficient removal and/or reabsorption of pharmacological agents. Since the majority of membrane transporters have broad substrate specificity, there is a significant risk for drug-drug interactions through competition for similar transport pathways. This article will focus on the cellular expression, localization, and transport properties of various renal drug transport systems (ie, organic anion, organic cation, nucleoside, and adenosine triphosphate [ATP]-dependent efflux transporters). Specific examples of drugs that are transported by each of these mechanisms will be provided. Clinically relevant drug-drug interactions involving renal drug transporters will be discussed to guide the clinician in understanding and preventing these interactions.

Key Words: renal proximal tubular cell • drug transport • tubular secretion • drug-drug interactions

Journal of Pharmacy Practice, Vol. 15, No. 6, 490-503 (2002)
DOI: 10.1177/089719002237667


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