title: Effect of CYP2C9*3 allele on the pharmacokinetics of naproxen in Korean subjects.
abstract: 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 concentration-time 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 AUC(0-infinity) (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.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hyung-Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seong-Ae
authors.initials: SA
authors.lastname: Byun
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Chang
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Young-Seo
authors.initials: YS
authors.lastname: Park
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D009288:Naproxen / Q000097:blood / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases