三七总皂苷注射液对大鼠肝CYP450酶的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (8): 849-854.

三七总皂苷注射液对大鼠肝CYP450酶的影响

李晓宇, 刘皋林, 周佳纯, 钱刚, 高君伟, 孙博, 郭彦王昆

上海交通大学附属第一人民医院药剂科, 上海 200080

收稿日期:2009-05-20 修回日期:2009-07-09 出版日期:2009-08-26 发布日期:2020-10-30
通讯作者: 刘皋林,男, 博士, 教授, 博士生导师, 研究方向:临床药理学与分子免疫干预机制。Tel:021-63240090-4408
作者简介:李晓宇, 男, 博士, 副教授, 研究方向:临床药理学与药物代谢动力学。Tel:021-63240090-4407 E-mail:xyllxb@yahoo.com.cn
基金资助:
中国博士后科学基金特别资助项目(200902245); 中国博士后科学基金面上项目 (20080430662); 上海市博士后科学基金项目(08R214138)

Experimental study on the effects of liver cytochrome protein 450 (CYP450) induced by panax notoginsenoside injection in rats

LI Xiao-yu, LIU Gao-lin, ZHOU Jia-chun, QIAN Gang, GAO Jun-wei, SUN Bo, GUO Yan-kun

Department of Pharmacy, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai200080, China

Received:2009-05-20 Revised:2009-07-09 Online:2009-08-26 Published:2020-10-30

摘要/Abstract

摘要： 目的: 在体酶探针法研究三七皂苷注射液对大鼠肝CYP450 酶的影响。方法: 连续 5周静脉注射给予大鼠20mg°kg^-1°d^-1 的三七总皂苷注射液后分别静注5.0mg/kg 的尼莫地平或灌胃20.0mg/kg的华法林钠, HPLC 法测定尼莫地平和华法林钠的血浆药物浓度, DAS 软件计算药动学参数,评价三七总皂苷注射液对大鼠CYP3A4、CYP2C9和CYP1A2 酶的影响, 采用双侧 t 检验方法对数据进行分析。结果: 建立并优化了大鼠体内尼莫地平和华法林钠的高效、快速和专属性强的HPLC 测定方法, 三七总皂苷注射液对尼莫地平和华法林钠在大鼠体内的药动学参数无显著性影响, 但长时间给予三七总皂苷注射液后有致尼莫地平AUC 升高而清除率下降的趋势, 也使华法林钠在大鼠体内的 t_max 、t_1/2、AUC 有升高的趋势。结论: 三七总皂苷对CYP3A4 、CYP2C9 和 CYP1A2可能有一定的抑制作用, 提示我们在临床上与上述酶底物合用时应注意药物相互作用出现的可能性。

关键词: 三七总皂苷, 尼莫地平, 华法林钠, 药代动力学, 药物相互作用

Abstract: AIM: Enzymes probes were employed for the study on the effects of liver CYP450 induced by panax notoginsenoside injection (PNSi) in rats. METHODS: PNSi was intravenous administered to rats for 5 weeks at the dosage of 20 mg°kg^-1°d^-1. Then 5.0 mg/kg dosage of nimodipine or 20.0 mg/kg dosage of warfarin sodium was given to rats via intrave-nous or intragastric administration, respectively at the last time of PNSi .HPLC wasemployed for the determi-nation of nimodipine and warfarin sodium in rat plasma .Pharmacokinetic parameters which simulated by DAS software were used for the evaluation on the effects of CYP3A4, CYP2C9 and CYP1A2 induced by PNSi . Two-sides of students test was used for datum analysis. RESULTS: Sensitive, rapid and specificity HPLC method was developed and validated for the determina-tion of nimodipine and warfarin in rat plasma success-fully .There were no markedly changes of pharmacoki-netic parameters of nimodipine or warfarin in rats in-duced by PNSi .However, the AUC and clearance of nimodipine displayed the tendency of increasing or de-creasing, respectively and the t_max , t_1/2 and AUC of warfarin sodium showed the tendency of increasing after intravenous administration of PNSi for a long time. CONCLUSION: PNSi showed potential inhibitory effect on the activities of CYP3A4, CYP2C9 and CYP1A2.Potential drug-drug interaction should be more cared when PNSi was co-administered with nimo-dipine or warfarin sodium in clinic .

Key words: panax notoginsenoside injection(PN-Si), nimodipine, warfarin sodium, pharmacokinetics, drug-drug interaction

中图分类号:

R969.1

李晓宇, 刘皋林, 周佳纯, 钱刚, 高君伟, 孙博, 郭彦王昆. 三七总皂苷注射液对大鼠肝CYP450酶的影响[J]. 中国临床药理学与治疗学, 2009, 14(8): 849-854.

LI Xiao-yu, LIU Gao-lin, ZHOU Jia-chun, QIAN Gang, GAO Jun-wei, SUN Bo, GUO Yan-kun. Experimental study on the effects of liver cytochrome protein 450 (CYP450) induced by panax notoginsenoside injection in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 849-854.

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