摘要
目的:采用不同种属肝微粒体,研究黄酮类化合物pongachin的体外代谢特性,明确参与pongachin代谢的CYP酶亚型。方法:选择UPLC-MS/MS测定方法,通过测定pongachin的剩余浓度,考察pongachin在人、大鼠和猴3个种属肝微粒体中的代谢稳定性,以及在大鼠肝微粒体中的代谢表型。结果:pongachin在人、大鼠和猴肝微粒体中t1/2分别为36.86、30.13和20.50 min;其清除率为人<大鼠<猴。在大鼠肝微粒体中,CYP2E1、CYP2C、CYP1A2对pongachin的代谢有较强抑制作用。结论:pongachin在人和大鼠肝微粒体中代谢稳定性较好(>30 min),且在人和大鼠肝微粒体中代谢相似,在临床上与其他抑制CYP2E1、CYP2C、CYP1A2代谢的药物合用时应注意药物间的相互作用。
Objective： By investigating the metabolic characteristics of pongachin in human, rat and monkey liver microsomes to identify CYP isozymes responsible for pongachin metabolism. Method： The metabolic stability and the CYP 450 phenotype of pongachin in liver microsomes were determined by UPLC-MS/MS method. Result： The corresponding t-/2 were 36.86, 30.13, 20.50 min for pongachin in human, rat and monkey liver microsomes, respectively, which indicated that the extent of metabolic rates in liver microsomes were in the order of human〈 in rat〈 in monkey. CYP2E1, CYP2C and CYP1A2 strong inhibited pongachin metabolism in rat microsomes. Conclusion： Pongachin showed good metabolic stability in human and rat liver microsomes （more than 30 min）. Meanwhile its metabolism in human was similar with that in rat. Potential drug-drug interaction should be vigilant when pongachin is co-administered with the medicines which can inhibit CYP2E1, CYP2C and CYP1A2.
出处
《中药与临床》
2016年第2期61-64,共4页
Pharmacy and Clinics of Chinese Materia Medica
基金
十二五重大新药创制(2012ZX09103101-066)
