抗肿瘤活性物CH330331在大鼠肝微粒体代谢及对药酶影响作用的研究  

Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes

作　　者：孙海燕[1] 和凡[2] 毕惠嫦[2] 黄文林[3] 黄民[2] 

机构地区：[1]深圳职业技术学院 [2]中山大学药学院临床药理研究所 [3]中山大学肿瘤防治中心

出　　处：《中国临床药理学与治疗学》2010年第6期607-612,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技重大专项经费资助(2009Z1X09304-003)

摘　　要：目的:体外研究大鼠肝微粒体中CH330331代谢的酶促动力学,并利用"Cocktail"探针药物模型,研究CH330331对主要CYP450亚型的体外抑制作用。方法:优化CH330331在大鼠肝微粒体中孵育的条件,并进行酶促动力学研究;探讨体外"Cocktail"探针药物模型的组成,并研究CH330331对CYP450亚型的体外抑制作用。结果:CH330331代谢的酶促动力学参数:最大反应速率(Vmax)为2.08μmol/(min.mgpro-tein),米氏常数(Km)为18.96μmol/L。CH330331对大鼠CYP1A2、CYP2C9和CYP2D6有弱抑制作用,对大鼠CYP2C19、CYP2E1和CYP3A4没有抑制作用。结论:临床使用中CH330331可以增加主要通过CYPCYP1A2,CYP2C9和CYP2D6代谢的药物浓度。AIM：To study the metabolic kinetics of CH330331 in rat liver microsome,and its inhibition on CYP450 subtypes in the ＂cocktail＂ models.METHODS：The incubation parameters in rat liver microsome were optimized and were the Michaelis-Menten parameters Km and Vmax estimated the component of probe inhibitors in ＂cocktail＂ models were also confirmed and the effect of CH330331 on main subtypes of cytochrome P450 studied.RESULTS：The Km and Vmax of CH330331 were 18.96 μmol/L and 2.08 μmol/（min·mg protein）,respectively.CH330331 had a weakly inhibition to the activity of CYP1A2,CYP2D6 and CYP2C9 but had no effect on CYP2C19,CYP2E1,and CYP3A4.CONCLUSION：CH330331 can increase the blood concentration of those drugs that are metabolized mainly by CYP1A2,CYP2D6 and CYP2C9.

关 键 词：CH330331 肝微粒体 CYP450 COCKTAIL 

分 类 号：R969[医药卫生—药理学]