Molecular mechanisms of transcriptional regulation of the intestinal and renal drug transporters in the normal and disease states.

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We demonstrated the basal transcriptional mechanisms of three kinds of drug transporters such as renal organic anion transporter 1 (OAT1). It was found that renal OAT3 is up-regulated during cholestasis, and is responsible for renal secretion of bile acids. We identified a SNP in the promoter region that affecting the promoter activity of H^+/organic cation antiporter (MATE1). Mate1 knockout mice were newly developed, and we clarified the pharmacokinetic roles of MATE1 in vivo. Heterozygous MATE variants could not influence the disposition of metformin in diabetic patients by the clinical pharmacokinetic study. These information should be useful to consider the pathophysiological roles and to apply the personalized pharmacotherapy of drug transporters