雌三醇在不同种属肝微粒体中体外代谢的研究

目的:采用体外肝微粒体孵育体系,研究雌三醇在大鼠、比格犬、人肝微粒体中酶代谢动力学及代谢产物。 方法:通过对雌三醇浓度、肝微粒体蛋白含量和孵育时间等条件的考察,优化雌三醇与肝微粒体的反应体系;应用LC-MS /MS定量检测孵育体系中的雌三醇及代谢产物,计算并比较代谢动力学参数。 结果:雌三醇在人、比格犬肝微粒体中不代谢,而在大鼠肝微粒体中可发生代谢,在雌雄大鼠的体外代谢参数T_1/2、CL_int、CL_h、K_m、V_max没有显著性差异;在雌雄大鼠肝微粒体代谢产物中均发现1个I相代谢产物,而且代谢产物的生成量不存在性别差异。 结论:雌雄大鼠的肝微粒体对雌三醇I相代谢途径基本相同。

Objective: To study in vitro estriol metabolism in rat,Beagle dog and human liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. Methods: The incubation systems of estriol with liver microsomes of three species were optimized in terms of estriol concentration,microsomal protein content and incubation time.Estriol and its metabolites were determined by LC-MS/MS method.The metabolizing parameters were calculated and compared. Results: Estriol was metabolized in the rat but not in Beagle dog and human liver microsomes.There was no distinctive difference for the metabolizing parameters of T_1/2,CL_int,CL_h,K_m and V_max between the female and male rat.One metabolite were found from I phase metabolism in both male and female rat liver microsomes and there were no distinctive difference between them. Conclusions: The results indicated that the major phase I metabolic pathway of estriol was basically similar in the male and female rat liver microsomes.

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