振源胶囊对辛伐他汀及其活性代谢物在大鼠体内的药动学影响

doi:10.5246/jcps.2020.07.047

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (7): 494-503.DOI: 10.5246/jcps.2020.07.047

振源胶囊对辛伐他汀及其活性代谢物在大鼠体内的药动学影响

袁叶, 于博, 张学琴, 李亚男, 王淑梅^*

河北医科大学第二医院, 河北石家庄 050000

收稿日期:2020-03-11 修回日期:2020-04-15 出版日期:2020-07-31 发布日期:2020-05-10
通讯作者: Tel.: +86-311-66003762, E-mail: Shumei-wang@163.com
基金资助:
Research Fund Project of health and Family Planning Commission of Hebei Province (Grant No. 20170571).

Effects of Zhenyuan capsule on the pharmacokinetics comparison of simvastatin and its active metabolites in rats

Ye Yuan, Bo Yu, Xueqin Zhang, Yanan Li, Shumei Wang^*

The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

Received:2020-03-11 Revised:2020-04-15 Online:2020-07-31 Published:2020-05-10
Contact: Tel.: +86-311-66003762, E-mail: Shumei-wang@163.com
Supported by:
Research Fund Project of health and Family Planning Commission of Hebei Province (Grant No. 20170571).

摘要/Abstract

摘要：

研究振源胶囊对辛伐他汀及其活性代谢产物辛伐他汀酸在大鼠体内的药动学影响, 为临床两药联合应用提供一定的理论依据。将24只雄性Wistar大鼠随机分成对照组与实验组, 每组12只, 对照组连续灌胃3‰羧甲基纤维素钠15天, 实验组连续灌胃振源胶囊混悬液15天。两组大鼠于16日清晨均灌胃给予等量辛伐他汀5.3 mg/kg。给药后不同时间点进行眼内眦静脉丛采血, 离心即得血浆样品。采用HPLC-MS/MS法测定辛伐他汀及辛伐他汀酸的血药浓度。应用DAS 2.1.1软件拟合药动学参数, SPSS 25.0软件分析统计学差异。结果发现,联用振源胶囊后, 辛伐他汀酸及辛伐他汀的药动学参数AUC_0–24与C_max均显著性减少(P<0.05)。振源胶囊可能对CYP3A4酶有一定促进作用, 可减少辛伐他汀及其代谢产物在大鼠体内的含量。

关键词: 振源胶囊, 辛伐他汀, 辛伐他汀酸, LC-MS/MS, 药动学

Abstract:

The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule, which is mainly used for the treatment of cardiovascular diseases. It has been reported that ginsenoside can affect the activity of CYP450 enzymes. Zhenyuan capsule and simvastatin may interact with each other through CYP3A4 mediation, then affect the efficacy and even produce adverse reactions. However, no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites. In this study, liquid chromatography–electrospray ionization–mass spectrometry (LC-MS/MS) was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats. Compared with the simvastatin alone, the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in AUC₀_–₂₄ and AUC₀_–_∞, and they were decreased in varying degrees (P<0.05). It appeared that the Zhenyuan capsule might increase the activity of CYP3A4 to some extent.

Key words: Zhenyuan capsule, Simvastatin, Simvastatin acid, LC-MS/MS, Pharmacokinetics

中图分类号:

R942

Supporting:

袁叶, 于博, 张学琴, 李亚男, 王淑梅. 振源胶囊对辛伐他汀及其活性代谢物在大鼠体内的药动学影响[J]. 中国药学(英文版), 2020, 29(7): 494-503.

Ye Yuan, Bo Yu, Xueqin Zhang, Yanan Li, Shumei Wang. Effects of Zhenyuan capsule on the pharmacokinetics comparison of simvastatin and its active metabolites in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(7): 494-503.

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振源胶囊对辛伐他汀及其活性代谢物在大鼠体内的药动学影响

Effects of Zhenyuan capsule on the pharmacokinetics comparison of simvastatin and its active metabolites in rats

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