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Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype
Author(s) -
Zhang Yifan,
Zhong Dafang,
Si Dayong,
Guo Yingjie,
Chen Xiaoyan,
Zhou Hui
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02223.x
Subject(s) - lornoxicam , pharmacokinetics , genotype , cyp2c9 , genotyping , pharmacology , polymorphism (computer science) , allele , chemistry , medicine , biochemistry , gene , analgesic
Aims To investigate the pharmacokinetics of lornoxicam and the relationship with CYP2C9 polymorphism in healthy Chinese subjects. Methods A single oral dose of 8 mg lornoxicam was administered to 18 healthy Chinese male subjects. Plasma was sampled for 24 h post dose, and plasma concentrations of lornoxicam were measured using a validated LC/MS/MS method. CYP2C9 genotype was determined by polymerase chain reaction‐based restriction fragment length polymorphism or by direct sequencing of the coding region of the CYP2C9 gene. Results Of the18 subjects, one subject was found to be a very poor metabolizer of lornoxicam with a long t 1/2 of 106 h, a low CL/F of 0.71 ml min −1 , and a high AUC 0–∞ of 187.6 µg ml −1 h. Genotyping studies revealed that this subject was heterozygous for CYP2C9 * 3 and a new variant CYP2C9 allele. Of the other 17 subjects, 13 were * 1/ * 1 carriers, three were * 1/ * 3 carriers, and one was a * 1/ * 2 carrier. Mean AUC 0–∞ values (95% confidence intervals) of lornoxicam were 9.25 (6.55, 11.95) vs. 4.75 (3.55, 5.95) µg ml −1 h in * 1 heterozygotes vs. * 1 homozygotes, and mean CL/F values were 14.8 (10.2, 19.4) vs. 32.9 (24.5, 41.3) ml min −1 , respectively ( P < 0.05 for both AUC and CL/F). Conclusions The results show that the pharmacokinetics of lornoxicam are dependent on CYP2C9 polymorphism. In particular, the presence of the CYP2C9 * 3 allele impairs the oral clearance of lornoxicam.