Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics.

Results: The frequencies of CYP2C9*1, *3, and *13 allele were 0.952 (95% confidence interval 0.945-0.959), 0.044 (95% CI 0.037- 0.051), and 0.005 (95% CI 0.003-0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13, and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918), 0.085 (95% CI 0.072-0.098), 0.009 (95% CI 0.005-0.013), and 0.001 (95% CI 0.000-0.002), respectively. In the pharmacokinetics studies, the AUC0-∞ of losartan in CYP2C9*3/*3 subject was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC0-∞ of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subject was only 12% of that in CYP2C9*1/*1 subjects. Conclusion: The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects.