关键词: 石斛碱, 肝微粒体, 代谢稳定性, 代谢产物, 种属差异

Abstract: In order to select the experimental animals for preclinical pharmacodynamics and toxicology,the characteristics of dendrobine metabolism in human liver microsomes were compared with the other species.Metabolic stability and metabolites of dendrobine were investigated in the liver microsomes of rat,mouse,rabbit,dog,guinea pig and human.The substrate depletion approach was used to evaluate the metabolic stability,and the half-life (t_1/2) was calculated in vitro.The differences in metabolic biotransformation of dendrobine were characterized by metabolite profiling.In the liver microsomal incubation systems of six species,the t_1/2 values for phase I were as follows:rabbit < guinea pig < rat < mouse < dog < human.Whereas for phase II,the metabolic rates were the slowest in the liver microsomes of human and guinea pig,and the fastest in mouse liver microsomes.In addition,the metabolites of dendrobine for phase I in human liver microsomes were similar to the mouse and dog liver microsomes incubation system.Based on the results of dendrobine metabolism in vitro,mouse and dog would be selected for the further metabolism study.

Key words: dendrobine, liver microsomes, metabolic stability, metabolite, species difference