采用重组人源CYP酶研究艾瑞昔布的体外羟基化代谢  

Investigation on the hydroxylation metabolism of imrecoxib in vitro by using recombinant human CYPs

作　　者：李强[1] 黄海华[2] 董宇[3] 钟大放[4] 

机构地区：[1]吉林大学生命科学学院 [2]沈阳药科大学微生物学教研室 [3]沈阳药科大学药物代谢与药物动力学实验室辽宁沈阳110016 [4]沈阳药科大药物代谢与药物动力学实验室辽宁沈阳110016

出　　处：《药学学报》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).

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.

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 

分 类 号：R969.1[医药卫生—药理学] R969.2[医药卫生—药学]