雷公藤甲素在大鼠肝微粒体中代谢及酶促反应动力学研究  

Metabolism and Enzyme Kinetics of Triptolide in Rat Liver Microsomes

作　　者：姚金成[1] 饶健[1] 曾令贵[1] 张陆勇[2] 江振洲[2] 何玲[2] 胡领[3] 赵绪元[3] 

机构地区：[1]湖南省药品审评认证与不良反应监测中心,长沙市410013 [2]中国药科大学国家新药筛选中心,南京市210009 [3]中南大学湘雅二医院,长沙市410011

出　　处：《中国药房》2010年第7期577-580,共4页China Pharmacy

基　　金：财政部行业科研专项“中药毒性的评价方法学研究和科学应用”资助项目(200707008);湖南省科技厅科技计划项目(2009SK3084)

摘　　要：目的:研究雷公藤甲素在大鼠肝微粒体中代谢及酶促反应动力学。方法:将雷公藤甲素与5种不同诱导剂(地塞米松(DEX)、苯巴比妥(PB)、β-萘黄酮(β-NF)、吡啶(PD))诱导的大鼠肝微粒体进行体外共孵育;并与8种选择性CYP酶抑制剂(酮康唑、醋竹桃霉素、磺胺苯吡唑、二乙基二硫代氨基甲酸酯(盐)、奎尼丁、呋拉茶碱、毛果芸香碱、奥芬那君)在空白肝微粒体中共孵育。采用液相色谱-质谱联用技术测定孵育后剩余雷公藤甲素的含量。结果:酮康唑和醋竹桃霉素能明显抑制雷公藤甲素的代谢;磺胺苯吡唑和奥芬那君对其代谢也有一定抑制作用,但不及酮康唑和醋竹桃霉素。结论:雷公藤甲素在大鼠肝微粒体中代谢主要由CYP3A介导,其次由CYP2C和CYP2B介导。OBJECTIVE： To investigate the enzyme kinetics of triptolide metabolism in rat liver microsomes. METHODS： The metabolism of triptolide was investigated with five kinds of hepatic microsomal incubates of rats pretreated by dexamethasone （DEX）, phenobarbital （PB）, 13-naphthoflavone（13-NF）,pyridine （PD）.and with blank hepatic microsomal incubates of rats pretreated by eight kinds of selective cytochrome P450 inhibitors such as ketoconzole, troleandomycin, isarol, diethydithio- carbamate, quinindium, furafyline, pilocarpine and orphenadrine. The residual of triptolide in rat hepatic microsomal was determ- ined by HPLC/MS. RESULTS： The metabolism of triptolide were significantly inhibited by ketoconazole and troleandomycin while sulfaphenazole and orphenadrine citrate salt showed inferior inhibitory effect on the metabolism of triptolide. CONCLUSION： CYP3A may be mainly involved in the metabolism of triptolide, CYP2C and CYP2B were secondary participant in the metabolism of triptolide.

关 键 词：雷公藤甲素 大鼠肝微粒体 体外代谢 酶促反应动力学 

分 类 号：R285[医药卫生—中药学] R97[医药卫生—中医学]