CYP2C9*3 and*13 alleles significantly affect the pharmacokinetics of irbesartan in healthy Korean subjects

Purpose: To evaluate the effects of two major polymorphisms of CYP2C9, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of irbesartan in healthy Korean volunteers. Methods: A single 150-mg oral dose of irbesartan was given to 28 Korean volunteers, who had different CYP2C9 genotypes (12, 10, and 6 carriers of CYP2C9*1/*1,*1/*3, and*1/*13 genotypes respectively). Irbesartan levels were analyzed using HPLC fluorescence in plasma samples collected up to 36 h after the drug intake. Results: Compared with CYP2C9*1 homozygous subjects, not only were the maximum plasma concentrations (C _max) of irbesartan in CYP2C9*1/*3 and*1/*13 subjects 1.56- and 1.50-fold higher (P = 0.001), but the half-lives were also 1.38- and 1.50-fold longer (P = 0.001). The area under the plasma concentration-time curve (AUC) was 1.64- and 1.79-fold higher (P < 0.001). The oral clearance of irbesartan was 39.3% and 44.0% lower in the CYP2C9*1/*3 and*1/*13 subjects respectively, than in the*1/*1 subjects (P < 0.001). Likewise, the increases in half-life and decreases in oral clearance observed in CYP2C9*1/*13 individuals were similar to those in participants expressing the CYP2C9*1/*3 genotype. Conclusions: CYP2C9 genetic polymorphisms markedly affected the pharmacokinetics of irbesartan in this study sample. The CYP2C9*3 and CYP2C9*13 alleles appear to be associated with the decreased metabolism of irbesartan.