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Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype
| Content Provider | Scilit |
|---|---|
| Author | Zhang, Yifan Zhong, Dafang Si, Dayong Guo, Yingjie Chen, Xiaoyan Zhou, Hui |
| Copyright Year | 2005 |
| Description | Journal: British journal of clinical pharmacology To investigate the pharmacokinetics of lornoxicam and the relationship with CYP2C9 polymorphism in healthy Chinese subjects. 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. Of the 18 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-infinity) of 187.6 microg 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-infinity) values (95% confidence intervals) of lornoxicam were 9.25 (6.55, 11.95) vs. 4.75 (3.55, 5.95) microg 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). 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884973/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2005.02223.x/pdf |
| Ending Page | 17 |
| Page Count | 4 |
| Starting Page | 14 |
| e-ISSN | 13652125 |
| DOI | 10.1111/j.1365-2125.2005.02223.x |
| Journal | British journal of clinical pharmacology |
| Issue Number | 1 |
| Volume Number | 59 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2005-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British journal of clinical pharmacology Clinical Pharmacokinetics Cyp2c9 Polymorphism |
| Content Type | Text |
| Resource Type | Article |
