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Effect of CYP2C9*3 Allele on the Pharmacokinetics of Naproxen in Korean Subjects
배정우,김지홍,장춘곤,박영서,이석용,최창익,김미정,김형지,변성애,창영순 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2
The genetically polymorphic CYP2C9 metabolizes many non-steroidal anti-inflammatory agents, including naproxen. This study examined the effects of a CYP2C9 genetic polymorphism on the pharmacokinetics of naproxen in Korean subjects. Twenty healthy male subjects carrying a CYP2C9*1/*1 (n=14) or CYP2C9*1/*3 (n=6) polymorphism were enrolled. After a single-dose of 275 mg naproxen Na, blood samples were collected at various times over a 72 h period and the plasma naproxen concentration was measured. The plasma concentration of naproxen was determined by HPLC analysis with UV detection, and the pharmacokinetic parameters were calculated. The mean plasma concentrationtime profiles of naproxen in the CYP2C9*1/*3 and CYP2C9*1/*1 individuals were similar. There were no significant differences in the pharmacokinetics of naproxen between CYP2C9*1/*1 and CYP2C9*1/ *3 genotypes. The AUC0-∞ (p = 0.759) and oral clearance (p = 0.823) of naproxen were also similar in individuals with CYP2C9*1/*3 and CYP2C9*1/*1. Overall, a genetic polymorphism of CYP2C9 does not significantly affect the pharmacokinetics of naproxen. Therefore, naproxen does not require a dose adjustment for individuals with the CYP2C9*1/*3 genotype.