title: Effects of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects.
abstract: The aim of this study was to investigate the impact of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9*1/*1 (n = 12) or CYP2C9*1/*3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4'-hydroxyflurbiprofen were measured by HPLC. AUCinf of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9*1/*3 individuals than in those with CYP2C9*1/*1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9*1/*3 individuals than in those with CYP2C9*1/*1. These results indicate that the individuals carrying of CYP2C9*3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Ji-Yeong
authors.initials: JY
authors.lastname: Byeon
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Se-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Uy-Dong
authors.initials: UD
authors.lastname: Sohn
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Lee
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001711:Biotransformation; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D008297:Male; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; C065522:4'-hydroxyflurbiprofen; D005480:Flurbiprofen; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9