摘要
目的探讨新型抗炎镇痛药艾瑞昔布在人体内的羟基化代谢酶。方法用体外重组的人源细胞色素P450(CYP)进行孵育代谢实验,液相色谱-多级质谱法分析代谢产物和残留的母体药物,利用整体归一化法对4种CYP酶的代谢作用大小进行评估。结果艾瑞昔布羟基化代谢可由CYP2C9,CYP2D6和CYP3A4催化,其各自作用大小分别为62.5%,21.1%和16.4%。结论CYP2C9为艾瑞昔布羟基化的主要代谢酶。
Aim To identify the drug-metabolizing enzymes involved in the hydroxylation of the new anti-inflammatory and anodyne imrecoxib. Methods Imrecoxib was incubated with heterologous expression human cytochrome P450 （rCYPs） in vitro, and metabolites and remained parent drug were detected with liquid chromatography-multistage mass spectrometry. The contribution of 4 CYPs in the hydroxylation metabolism of imrecoxib was evaluated by total normalized rate （TNR） method. Results Imrecoxib is metabolized by CYP2Cg, CYP2D6 and CYP3A4, with the rate of 62.5%, 21.1% and 16.4%, respectively. Conclusion CYP2C9 is the major enzyme involved in imrecoxib hydroxylation metabolism.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第10期912-915,共4页
Acta Pharmaceutica Sinica
基金
国家高技术研究发展计划(863计划)课题(2003AA2Z347C).
关键词
细胞色素P450
羟基化代谢
艾瑞昔布
液相色谱-多级质谱法
整体归一化
cytochrome P450
hydroxylation metabolism
imrecoxib
liquid chromatography-multistage mass spectrometry
total normalized rate
