【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。更多还原

【Abstract】 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),β-naphthoflavone(β-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,diethydithiocarbamate,quinindium,furafyline,pilocarpine and orphenadrine.The residual of triptolide in rat hepatic microsomal was determined 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.更多还原