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普鲁卡因胺经羧酸酯酶1对咪达普利代谢的影响 被引量：1

Effect of Procainamide on the Metabolism of Imidapril Through Carboxylesterase 1(CES1)
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摘要 目的:研究普鲁卡因胺经羧酸酯酶1(CES1)影响咪达普利代谢的作用。方法:进行体外大鼠肝微粒体酶孵育实验,通过测定CES1特异性底物咪达普利的代谢产物咪达普利拉的含量,来研究普鲁卡因胺对CES1活性的影响;将12只SD大鼠随机分为两组,分别给予生理盐水和普鲁卡因胺(50mg·kg^(-1)),连续4 d,随后灌胃给予咪达普利(10mg·kg^(-1)),于给药后不同时间点采集血样,采用LC-MS/MS法测定血浆中咪达普利拉的含量,计算药动学参数,来研究普鲁卡因胺对咪达普利在大鼠体内代谢的影响。结果:在体外研究中,普鲁卡因胺对CES1的调节呈现剂量依赖型抑制特征。体内研究发现,普鲁卡因胺显著降低咪达普利拉AUC_(0-24h),AUC_(0-∞)和C_(max)。结论:普鲁卡因胺显著抑制CES1的活性,从而抑制咪达普利拉的形成,对酯类前药代谢的研究有一定的意义。 Objective： To evaluate the effect of procainamide on the metabolism of imidapril through Carboxylesterase 1 （ CES1 ）. Method： The effect of procainamide on CES1 was investigated by the hydrolysis of imidapril in cuhured rat hepatocytes. Twelve rats were divided into two groups：imidapril ＋ 0. 9% saline solution, imidapril ＋ procainamide （50 mg·kg^-1 ）. Plasma concentration of imidaprilat was determined by LC-MS/MS. Result： In vitro study, procainamide-mediated inhibition of CES1 exhibited a concentration-dependent manner. In vivo ,AUC0.24h ,AUC0-∞ and Cmax of imidaprilat were decreased significantly. Conclusion： The activity of CES1 and the formation of imidaprilat were inhibited obviously by procainamide which had certain significance in metabolism of ester-prodrugs.
作者 刘东 徐艳娇 任秀华 向道春 张程亮
机构地区 华中科技大学同济医学院附属同济医院药学部
出处 《中国药师》 CAS 2011年第1期6-8,共3页 China Pharmacist
基金 中央高校基本科研业务费资助 HUST(编号:2010JC057)
关键词 羧酸酯酶1 普鲁卡因胺 咪达普利 代谢 Carhoxylesterasel Procainamide Imidapril Metabolism
分类号 R969.1 [医药卫生—药理学]
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参考文献8

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同被引文献18

  • 1王引利,王伟,杜传礼.咪达普利的药理学特性和临床治疗意义[J].心血管病学进展,2005,26(1):21-23. 被引量：6
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  • 6Yamada Y, Ohashi R, Sugawara Y, et al. Metabolic fate of the new angiotensin-converting enzyme inhibitor imi- dapril in animals. 5th communication: isolation and iden- tification of metabolites of imidapril in rats, dogs, and monkeys[J]. Arzneimittelforschung, 1992, 42 (4) : 490.
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中国药师
2011年 第1期

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