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 vivtro by using recombinant human CYPs

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。

Abstract: AimTo identify the drug-metabolizing enzymes involved in the hydroxylation of the new anti-inflammatory and anodyne imrecoxib. MethodsImrecoxib was incubated with heterologous expression human cytochrome P450 (rCYPs) in vivtro, 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 CYP2C9, CYP2D6 and CYP3A4, with the rate of 62.5%, 21.1% and 16.4%, respectively. ConclusionCYP2C9 is the major enzyme involved in imrecoxib hydroxylation metabolism.