目的对甘草苷的苷元甘草素在体外不同种属肝微粒体中的代谢差异进行比较研究,为甘草苷的进一步研究开发提供参考依据。方法甘草素与不同种属,包括大鼠、小鼠、人、犬及猴的肝微粒体进行孵育,比较其代谢稳定性和代谢转化情况。代谢稳定性通过底物消除法分析甘草素的剩余底物浓度水平随时间的变化,计算体外消除半衰期(t1/2)。进一步对甘草素在肝微粒体孵育后生成的代谢产物谱以及代谢途径进行分析。结果在I相肝微粒体孵育体系中,甘草素在5个种属肝微粒体中发生代谢的t1/2依次为大鼠<小鼠<人<猴<犬;在II相肝微粒体孵育体系中,甘草素代谢都非常快,除小鼠外,均在5 min内下降50%以上。甘草素与人肝微粒体进行II相孵育产生的代谢产物谱和猴的相同,其余种属则与人有明显不同。结论甘草素在猴肝微粒体中的代谢稳定性和代谢产物谱均与人最相似,其次为犬肝微粒体,大鼠和小鼠则与人存在明显差异。在进一步的临床前药代和毒理研究中可选用猴或犬作为模型动物。 Objective To compare the metabolic differences of glycyrrhizin glycyrrhizin in different species of liver microsomes in vitro and provide reference for the further research and development of liquiritin. Methods Liquiritigenin was incubated with liver microsomes from different species, including rats, mice, humans, dogs and monkeys. The metabolic stability and metabolic transformation were compared. Metabolic Stability The in vitro elimination half-life (t1 / 2) was calculated by analyzing the change in the remaining substrate concentration level of liquiritigenin with substrate elimination method. Further analysis of metabolic spectrum and metabolic pathway of glycyrrhizin after incubation with liver microsomes was carried out. Results In the phase I liver microsomal incubation system, the t1 / 2 of the metabolism of liquiritigenin in five species of liver microsomes was in the order of rat