title: Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes.
abstract: OBJECTIVE
  This study was conducted to examine differences in flurbiprofen metabolism among individuals with the CYP2C9*1/*1, *1/*2, and *1/*3 genotypes.
  
  
  METHODS
  Fifteen individuals with the CYP2C9*1/*1 ( n=5), *1/*2 ( n=5), and *1/*3 ( n=5) genotypes received a single 50-mg oral dose of flurbiprofen. Plasma and urine samples were collected over 24 h, and flurbiprofen and 4'-hydroxyflurbiprofen pharmacokinetic data were compared across genotypes.
  
  
  RESULTS
  CYP2C9 genotype was a significant predictor of flurbiprofen metabolism and accounted for 59% of the variability in flurbiprofen AUC(0- infinity ), and approximately 50% of the variability in flurbiprofen oral clearance, formation clearance to 4'-hydroxyflurbiprofen, and the 0 to 24-h urinary metabolic ratio of flurbiprofen to 4'-hydroxyflurbiprofen. Flurbiprofen AUC(0- infinity )was significantly higher and all measures of flurbiprofen clearance were significantly lower in the CYP2C9*1/*3 individuals than in those with *1/*1. Significant differences in these parameters were not detected between *1/*2 subjects and *1/*1 subjects.
  
  
  CONCLUSIONS
  CYP2C9 genotype is a significant predictor of flurbiprofen disposition in humans by altering CYP2C9-mediated metabolism and reducing systemic clearance. The effects are most pronounced in individuals carrying the *3 allele.
authors.affiliation: Division of Pharmacotherapy, University of North Carolina at Chapel Hill, NC 27599-7360, Chapel Hill, USA. craig_lee@unc.edu
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lee
authors.forename: John A
authors.initials: JA
authors.lastname: Pieper
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Frye
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hinderliter
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Blaisdell
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005838:Genotype; D006801:Humans; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C065522:4'-hydroxyflurbiprofen; D005480:Flurbiprofen; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases