苗药红花龙胆有效成分芒果苷在不同物种肝微粒体中的代谢稳定性研究  

Study on Metabolic Stability Rate of Mangiferin in Different Species of Liver Microsomes

作　　者：包江平 赵琳珺 郭妍如 夏媛媛 于佳 常博韬 罗君 BAO Jiang-ping;ZHAO Lin-jun;GUO Yan-ru;XIA Yuan-yuan;YU Jia;CHANG Bo-tao;LUO Jun(First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 55001,China;Xintian Community Health Service Center in Guiyang,Guiyang Guizhou 550018,China;Guizhou University of Traditional Chinese Medicine,Guizhou Guiyang 550025 China)

机构地区：[1]贵州中医药大学第一附属医院,贵阳550001 [2]贵阳市乌当区新天社区卫生服务中心,贵阳550018 [3]贵州中医药大学,贵阳550025

出　　处：《时珍国医国药》2021年第8期1874-1877,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家中医药管理局中药特色技术传承人才项目(国中医药办人教函[2018]204号);贵州省科学技术厅科技支撑计划项目(黔科合支撑[2018]2772);贵州省“十四五”中医药、民族医药重点学科—临床中药学;贵州省中医肿瘤传承与科技创新人才团队(黔科合平台人[2020]5013);贵州省贵阳市科技局(筑科合同[2019]9-2-11;筑科合同[2019]9-2-32);贵州省科学技术厅(黔科中引地[2020]4001号)。

摘　　要：目的探讨芒果苷在SD大鼠、Beagle犬和人3个种属肝微粒体中的代谢稳定性。方法应用还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)启动的I相代谢的体外肝微粒体孵育体系,将芒果苷与不同种属肝微粒体共同孵育,采用UPLC-MS/MS法测定芒果苷的质量浓度,考察其代谢稳定性及体外动力学参数。结果在I相肝微粒体孵育体系中,芒果苷在SD大鼠、Beagle犬和人3个种属肝微粒体中体外消除半衰期T_(1/2)分别为866.25 min、845.12 min、924.00 min;体外固有清除率(CL_(int))分别为1.60μL/min/mg、1.64μL/min/mg、1.50μL/min/mg。结论芒果苷在大鼠、Beagle犬以及人的肝微粒体中的I相代谢均稳定,3个种属之间不存在显著差异,后续的实验可以考虑用SD大鼠来研究药物的代谢,为进一步的临床前药代动力学和毒理研究中可选用的模型动物提供依据。Objective To investigate the metabolic stability of mangiferin in liver microsomes of SD rats,Beagle dogs and humans.Methods Mangiferin was incubated with different species liver microsomes by using in vitro phase I liver microsome incubation system that initiated by reduced nicotinamide adenine dinucleotide phosphate(NADPH).The mass concentration of mangiferin was determined by UPLC-MS/MS to investigate its metabolic stability and in vitro kinetic parameters.Results The t_(1/2)of mangiferin were 866.25,845.12 and 924.00 min in SD rat,Beagle dog and human liver microsomes.CL_(int)were 1.60μL,1.64μL,1.50μL/(min/mg),respectively.Conclusion Phase I metabolism of mangiferin was stable in liver microsomes from SD rats,Beagle dogs,as well as humans,with no significant differences among these three species.SD rats can be considered to be the model animal in the further preclinical pharmacokinetics and toxicological studies.

关 键 词：芒果苷 肝微粒体 UPLC-MS/MS 代谢稳定性 

分 类 号：R285.5[医药卫生—中药学]