二氢吡啶类钙通道阻滞药对人肝微粒体中氯吡格雷代谢的抑制作用

发布时间：2018-02-01 11:49

本文关键词： 二氢吡啶类氯吡格雷人肝微粒体代谢相互作用　出处：《中国药房》2015年10期 　论文类型：期刊论文

【摘要】：目的:研究二氢吡啶类(DHPs)钙通道阻滞药硝苯地平、氨氯地平、非洛地平对人肝微粒体中氯吡格雷代谢的影响,为临床合理用药提供参考。方法:采用人肝微粒体体外代谢模型,将0.1、1、5、10、25、50、100、200μmol/L的硝苯地平、氨氯地平、非洛地平分别与氯吡格雷(20μmol/L)在人肝微粒体中进行共孵育,孵育15 min后加入5倍体积的含内标氯雷他定的冰乙腈溶液(内标终质量浓度为500 ng/ml)终止反应。沉淀蛋白后取上清液,采用超高效液相色谱-质谱(UPLC-MS)法检测氯吡格雷的浓度,以不加DHPs药物为阴性对照计算各DHPs药物作用下氯吡格雷的代谢抑制率。结果:硝苯地平、氨氯地平、非洛地平对人肝微粒体中氯吡格雷的代谢均有一定程度的抑制作用,但200μmol/L浓度时代谢抑制率仍不及50%,提示半数抑制浓度均大于200μmol/L。结论:DHPs药物能抑制人肝微粒体中氯吡格雷的代谢,但抑制作用不强。提示DHPs药物不与氯吡格雷发生相互作用,不会影响两者临床联合使用。
[Abstract]:Objective: to study the effect of nifedipine, amlodipine and felodipine on the metabolism of clopidogrel in human liver microsomes. Methods: the in vitro metabolic model of human liver microsomes was used. Amlodipine and felodipine were co-incubated with clopidogrel 20 渭 mol / L in human liver microsomes. After incubation for 15 min, 5 times volume of glacial acetonitrile solution containing internal standard loratadine (final mass concentration of internal standard was 500ng / ml) was added to terminate the reaction. The supernatant was obtained after precipitation of protein. The concentration of clopidogrel was determined by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS). The metabolic inhibition rate of clopidogrel was calculated with no DHPs as negative control. Results: nifedipine and amlodipine were used to inhibit the metabolism of clopidogrel. Felodipine inhibited the metabolism of clopidogrel in human liver microsomes to some extent, but the inhibitory rate was still less than 50% at 200 渭 mol/L concentration. The results indicated that the half inhibitory concentration was more than 200 渭 mol / L. ConclusionThe drug of w DHPs can inhibit the metabolism of clopidogrel in human liver microsomes. But the inhibitory effect is not strong. It suggests that DHPs does not interact with clopidogrel and does not affect the clinical use of both drugs.
【作者单位】：常州市第一人民医院药剂科;常州市第二人民医院药剂科;
【基金】：常州市卫生科研项目(No.201006)
【分类号】：R969
【正文快照】： 肝微粒体酶又称肝药酶,主要存在于肝细胞内质网中。该系统中的主要酶为细胞色素P450,又称为细胞色素P450混合功能氧化酶系(简称CYP),是肝内最重要的药物代谢酶,参与绝大多数药物和部分内源性物质的体内代谢。其中,CYP3A4约占人肝脏中细胞色素酶总量的30%,该酶的活性容易受到抑

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