昆明医科大学学报2025，Vol.46Issue(2)：17-22,6.DOI:10.12259/j.issn.2095-610X.S20250203
法莫替丁对酒石酸美托洛尔在人肝微粒体中代谢的影响
The Effect of Famotidine on the Metabolism of Metoprolol Tartrate in Human Liver Microsomes
摘要
Abstract
Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate.Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system.A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration;using the substrate depletion method,the enzymatic reaction kinetics parameters of metoprolol tartrate(such as Vmax and Km).Series concentrations of famotidine were co-incubated with metoprolol tartrate,and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism.Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes,with an optimal protein concentration of 1.0 mg/mL.The enzymatic reaction kinetics parameters were Vmax=0.07 µmol/min/mg protein and Km=7.84 µmol/L.Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system,suggesting that the combination of these two drugs may be relatively safe.关键词
酒石酸美托洛尔/法莫替丁/人肝微粒体/LC-MS/MS/酶促反应动力学Key words
Metoprolol tartrate/Famotidine/Human liver microsomes/LC-MS/MS/Kinetics of enzymatic reactions分类
临床医学引用本文复制引用
徐冉,冯恩富,熊宇宇,朱加德,何功浩..法莫替丁对酒石酸美托洛尔在人肝微粒体中代谢的影响[J].昆明医科大学学报,2025,46(2):17-22,6.基金项目
国家自然科学基金(81960664) （81960664）
云南省教育厅科学研究基金(2024Y254) （2024Y254）
云南省中青年学术和技术带头人后备人才项目(202405AC350037) （202405AC350037）
云南省科技厅-昆明医科大学应用基础研究联合专项基金(202101AY070001-300) （202101AY070001-300）
