Organic anion transporters and their implications in pharmacotherapy.

Organic anion transporters play an essential role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. The expression and activity of these transporters is influenced by several conditions, including transcriptional regulation, gender-dependent regulation, and genetic variation. In addition, the interaction of these transporters with several drugs and endogenous substrates has been well documented and may play a significant role in drug disposition and development of various disease states, such as nephrotoxicity and familial idiopathic hypouricemia. Members of this family of transporters have been localized mainly to the renal epithelia of various species. Much of the early research in this field has focused on their role in renal drug transport, yet increasing research on this family of transporters has localized them to various other epithelial tissues, including liver, brain, and placenta. Thus, an understanding of the role of these transporters in drug interaction and disposition in the kidney and other tissues may help in the determination of individual drug response, susceptibility to drug toxicity, and chemical carcinogenesis. This review seeks to summarize current knowledge of the molecular function and substrate profile of cloned organic anion transporters and to discuss recent progress in the understanding of the impact of interindividual variability, transcriptional regulation, and tissue distribution on individual drug response.