Drugdrug interactions involving membrane transporters in the human kidney

Abstract

The kidneys play a critical role in the elimination of xenobiotics. Factors affecting the ability of the kidney to eliminate drugs may result in marked changes in the pharmacokinetics of a given compound. Drugdrug interactions due to competitive inhibition of renal organic anion or cation secretion systems have been noticed clinically for a long time. However, our understanding of the physical sites of interactions, that is, the specific transport proteins that the interacting drugs act on, has just begun very recently. This review summarises the latest progress in molecular identification and functional characterisation of major drug transporters in the human kidney. In particular, the review focuses on relating cloned renal drug transporters to clinically observed drugdrug interactions. The authors opinion on the current status and future directions of research in these areas is also offered.

Keywords::

• drug interactions
• drug transporters
• kidney
• organic anion transporters
• organic cation transporters
• pharmacokinetics

Acknowledgements

This work was supported by National Institutes of Health Grants GM066233 (JW) and AT002077 (GDA). ML is a recipient of the William E Bradley Endowed Fellowship from School of Pharmacy, University of Washington.