The influences of

To investigate the combined effects of and genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their c.521T>C and c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model. The c.521T>C variant significantly increased exposure to simvastatin acid by around 40% (p < 0.05), similar to that caused by the amlodipine pretreatment. The gene showed no influence on exposure to simvastatin or simvastatin acid. Only , not genotype, is likely to be associated with simvastatin-induced myopathy. genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors.