Transporters involved in the elimination of drugs in the kidney: Organic anion transporters and organic cation transporters

Transporters in the kidney mediate the secretion or reabsorption of many co mpounds and thereby influence the plasma levels of their substrates. Organi c anion transporters and organic cation transporters are two major classes of secretory transporters in the mammalian kidney. During the past decade, significant progress has been made in the cloning, functional expression, a nd initial characterization of these transporters. To date, five organic ca tion transporters and nine organic anion transporters have been cloned. In this review, we summarize the available data on organic anion and organic c ation transporters, focusing in particular on their molecular characteristi cs, tissue distribution, and inhibitor and substrate selectivities. Current ly we have a good understanding of the inhibitor selectivities for most of these transporters, and with the development of more robust assays, we will soon have a better understanding of their substrate selectivities. Based o n the available data, summarized in this review, it appears that many compo unds interact with multiple transporters. Futhermore, there appears to be s ubstantial overlap in the selectivities of organic cation transporters, and the same appears true for organic anion transporters. At the present time, it is unclear what; the roles of these multiple transporters are in renal drug elimination. With the development of new assays, reagents, and experim ental methods, we will soon have a better understanding of the roles of eac h transporter isoform in the renal elimination of drugs. (C) 2001 Wiley-Lis s, Inc. and the American Pharmaceutical Association J Pharm Sci 90:397-421, 2001.