Evaluation of drug interaction and interindividual differences of renal drug excretion based on the genetic polymorphism analysis

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Drug transporters expressed in the kidney play important roles for elimination of number of hydrophilic compounds such as drugs, toxins and endogenous compounds. In the present study, we evaluated interindividual differences of pharmacokinetic (PK) properties based on the genetic information and expression profiles of human renal drug transporters.We have identified and characterized novel renal specific transporters hOCT2-A and NaGLT1. Expression profiles for various drug transporters such as organic ion transporters in the human kidney were constructed. We have identified single nucleotide polymorphisms for coding region (cSNPs) of hOCT1 and hPEPT2 with decreasing the functional activities, but the appearance rates of these SNPs were very low. The correlation analyses between expression of drug transporters and PK properties in renal failure patients and model animals indicated that expression levels of renal drug transporters are responsible for interindividual differences of drug renal excretion. These findings could provide information for quantitative prediction and evaluation of PK based on the expression levels of renal drug transporters.