title: Effect of the CYP2C9*3 allele on lornoxicam metabolism.
abstract: BACKGROUND
  We investigated whether the CYP2C9 genotypes would affect lornoxicam metabolism in healthy volunteers.
  
  
  METHODS
  Twelve healthy volunteers who had been genotyped for CYP2C9 gene were selected to participate in our study. After 8 mg lornoxicam was taken, blood samples were drawn from 0 to 36 h. The plasma concentrations of lornoxicam and 5'-hydroxylornoxicam were determined by HPLC method. 5'-hydroxylornoxicam was purified from rabbits'urine by semi-preparative HPLC.
  
  
  RESULTS
  Lornoxicam and 5'-hydroxylornoxicam both exhibit CYP2C9 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of lornoxicam increased by 60 +/- 9.78% (P <0.05) and the AUC of 5'-hydroxylornoxicam decreased by 65 +/- 11.75% (p <0.001) in heterozygous CYP2C9*1/*3 subjects (n=6) compared with CYP2C9*1/*1 group (n=6). t1/2 value of lornoxicam and 5'-hydroxylornoxicam prolonged by 39 +/- 8.35% and curtailed by 59 +/- 6.83% respectively in CYP2C9*1/*3 subjects. But no significant differences in Tmax of lornoxicam and 5'-hydroxylornoxicam were observed between these 2 genotypes. In addition, for the first time we exploit the purification method for 5'-hydroxylornoxicam from rabbits' urine.
  
  
  CONCLUSIONS
  The CYP2C9*3 allele significantly affected the metabolism of lornoxicam. The pharmacokinetic parameters of both lornoxicam and 5'-hydroxylornoxicam were significantly different between these 2 genotypes.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Ouyang
authors.forename: Chen-hui
authors.initials: CH
authors.lastname: Luo
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiu
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: He
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006574:Heterocyclic Compounds, 2-Ring / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011725:Pyridines / Q000652:urine; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C509590:5'-hydroxylornoxicam; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006574:Heterocyclic Compounds, 2-Ring; D011725:Pyridines; D010894:Piroxicam; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C059451:lornoxicam