Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two sepa¬rate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 signifi¬cant SNPs (P < 0.01) in Cmax, 135 significant SNPs (P < 0.01) in Tmax and 85 significant SNPs (P < 0.01) in AUCinf from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on Cmax and AUCinf. These results could provide information of possible candidate genes for personalized simvastatin therapy. KCI Citation Count: 2