S6 Renal Transporters: Mediators of Drug Disposition and Action

Kathleen M. Giacomini , Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA

Renal transporters play a critical role in drug disposition and pharmacologic effect. In particular, organic anion and cation transporters (OATs and OCTs) in the SLC22 family, localized to the basolateral membrane work together with transporters in the SLC47 family (multi-drug and toxin extrusion transporters, MATEs) on the apical membrane to mediate transepithelial flux. The renal secretion of a drug can be modulated by many factors including concomitant medications, genetic variants in renal drug transporters, and kidney dysfunction, which results in accumulation of uremic solutes that may inhibit renal transporters. In this presentation, I will describe work in our laboratory focused on renal drug transporters including both organic anion and cation transporters. I will present research on genetic variants in renal drug transporters and their effects on the levels of endogenous metabolites with a focus on discovery of potential biomarkers of transporter-mediated drug-drug interactions. In addition, I will describe how uremic solutes that accumulate in the plasma of patients with kidney dysfunction inhibit renal transporters leading to potential effects on renal drug clearance. Finally, I will describe how organic anion transporters in the kidney have evolved during primate evolution, which has important implications to interpretation of data from preclinical animal species.