| 郭峰 李燕娜 毛玉昌 沈智杰 徐德铎 侴桂新 王肖龙 胡卓汉.中药降脂方与阿托伐他汀代谢性相互作用的体外研究[J].,2014,14(9):1611-1615 |
| 中药降脂方与阿托伐他汀代谢性相互作用的体外研究 |
| Metabolismbased Herb-Drug Interaction-Lipid-lowering Herbsand Atorvastatin in vitro |
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| DOI： |
| 中文关键词: 降脂中药 阿托伐他汀 细胞色素P450 药物相互作用 |
| 英文关键词: Lipid-lowering herbs Cytochrome P450 CYP 3A4 inhibition herb-drug interaction |
| 基金项目:国家十一五科技重大专项（2008ZX10501） |
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| 中文摘要: |
| 目的：本研究旨在评估降脂中药复方2（Fang-2）及其6 个饮片（虎杖、泽泻、甘草、苍术、厚朴和夏枯草）的水提物对肝脏细胞
色素CYP3A4 的抑制作用，及对阿托伐他汀的代谢性药物相互作用。方法：（1）应用中药标准化制备技术，制备降脂中药复方2及
其6 个饮片的水提物；采用超速离心法制备肝微粒体。（2）评价降脂中药复方2 及其饮片对CYP 3A4 抑制作用。（3）评价降脂中药
复方2 及其饮片的水提物对阿托伐他汀的代谢的影响。结果：（1）体外实验的结果提示复方2 的水提物显著地抑制了微粒体
CYP3A4 的活性，其IC50 值为9.884 mg/mL。虎杖水提物对微粒体CYP3A4 的活性具有显著的抑制作用，其IC50 值为0.5491
mg/mL。（2）阿托伐他汀是首过代谢CYP3A4 的底物，在肝脏微粒体中大于70%的母体被代谢，其体外清除率Clint 和半数清除时
间分别为41.10 mL/mg/min 和60.43分钟。降脂中药复方2水提物与肝微粒体孵育后，阿托伐他汀的首过代谢显著减慢。降脂中
药复方2 及其6 个饮片水提取物对CYP3A4 的抑制强度与避免阿托伐他汀首过代谢的潜力成正比。结论：本文首次应用体外方
法研究了在临床上共同使用与PCI术后的阿托伐他汀和降脂中药复方2 之间的代谢性相互作用，揭示了后者及其饮片通过抑制
CYP3A4 改善了前者的强烈的首过代谢，从而可能优化临床治疗方案。 |
| 英文摘要: |
| Objective:To investigate the metabolismbased herb-drug interaction between AVT and lipid-lowering Herb Medicine
(Fang-2) and its six individual herbs (Rhizoma Et Radix Polygoni Cuspidati, Rhizoma Alismatis, Rhizoma Atractylodis, Radix Et Rhizoma
Glycyrrhizae, Cortex Magnoliae Officinalis, and Spica Prunellae) by using in vitro technologies.Methods:Results:(1) The test articles of herbs
were prepared by a standard procedure using liquid extraction. (2) CYP3A4 inhibition study: Human and rat liver microsomes were
incubated with extract of Fang-2 or its individual herb at 37℃ for 15 minutes, and then with testosterone, probe substrate of CYP3A4 in
the presence of beta-NADPH. Enzyme activity of CYP3A4, 6beta-hydroxylation of testosterone was quantified by using LC-MS/MS. (3)
Herb-Drug interaction study: Liver microsomes were preincubated with extract of Fang-2 or its individual herb at 37℃ for 15 minutes,
and then with AVT in the presence of beta-NADPH. Parent depletion of AVT was quantified by using developed LC-MS/MS. Methods.CYP3A4 inhibition: Fang-2 showed inhibitive potential on CYP3A4 activity with IC50 of 9.884 mg/mL. (2) AVT was extensively
depleted by the 1st pass metabolism with intrinsic clearance rate (Clint) of 41.10 ml/mg/min and T1/2 of 60.43 min in liver
microsomal incubation. The parent depletion of AVT was affected by preincubation with Fang-2. The inhibition of CYP3A4 by Fang-2
and its herbs was correlated with their preventing AVT from 1st pass metabolism by Fang-2 and its element positively.Conclusion:The
article first studied the metabolism based herb-drug interaction between AVT and lipid-lowering herbs by using in vitro technologies.
Furth investigation for metabolism based Herb-Drug interaction between Fang-2 and AVT will have significant clinical benefits in
cardiovascular clinical pharmacology. |
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