Effect of the CYP2C9*3 allele on lornoxicam metabolism.
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.
Liu
Ya-Li
YL
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology Central South University, Changsha, Hunan 410078, PR China.
Zhang
Wei
W
Tan
Zhi-Rong
ZR
Ouyang
Dong-Sheng
DS
Luo
Chen-hui
CH
Liu
Zhao-Qian
ZQ
Qiu
Yu
Y
Chen
Yao
Y
He
Yi-Jing
YJ
Zhou
Gan
G
Zhou
Hong-Hao
HH
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
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