枸杞多糖对多柔比星犬药代动力学的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (3): 246-253.

枸杞多糖对多柔比星犬药代动力学的影响

余健, 辛艳飞, 顾利强, 高海燕, 张升, 由振强, 温磊, 陈国灿, 陈云祥, 宣尧仙

浙江省医学科学院安全性评价研究中心,杭州 310013,浙江

收稿日期:2013-03-26 修回日期:2014-02-16 出版日期:2014-03-26 发布日期:2014-04-10

Effects of Lycium barbarum Polysaccharide on doxorubicin pharmacokinetics in dogs

YU Jian, XIN Yan-fei , GU Li-qiang, GAO Hai-yan, ZHANG Sheng, YOU Zhen-qiang, WEN Lei, CHEN Guo-can, CHEN Yun-xiang, XUAN Yao-xian

Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013,Zhejiang,China

Received:2013-03-26 Revised:2014-02-16 Online:2014-03-26 Published:2014-04-10
Contact: Xin Yan-fei, male, correspondece author, investigator, research area: pharmacokinetic.Tel: 0571-87568012 E-mail:xinyanfei@gmail.com。Xuan Yao-xian, female, correspondece author, investigator, Tel: +86-571-87568016 E-mail: nndsvc@mail.hz.zj.cn
Supported by:
Zhejiang Provincial Bureau of Traditional Chinese Medicine (2013ZZ003);the Sciences Technology Department of Zhejiang Province (2012C37098,2013F20005) and Ministry of Science and Technology of China (2011ZX09301-003)

摘要/Abstract

摘要： 目的: 研究枸杞多糖对多柔比星在比格犬中的药代动力学性质的影响。方法: 8只比格犬连续 12 d 给予枸杞多糖胶囊(20 mg/kg)或空胶囊,在第7天所有犬均静脉注射给予多柔比星(1.5 mg/kg),本研究使用高效液相-荧光检测器对多柔比星的血药浓度进行检测。同时,本研究还对多柔比星对犬CYP3A活力的影响进行评价。结果: 与单独给予多柔比星相比,联合给予枸杞多糖没有改变例如曲线下面积和清除率在内的多柔比星的药代动力学性质。但是,研究结果表明,枸杞多糖会抑制CYP3A的活性,CYP3A是多柔比星在犬中的重要代谢酶。结论: 在给予多柔比星同时联合口服给予枸杞多糖不会影响多柔比星的药代动力学性质,但是会抑制CYP3A的活性。

关键词: 枸杞多糖, 心脏毒性, 药物相互作用, 本文编辑:钟正灵

Abstract: AIM: To investigate whether Lycium barbarum Polysaccharide (LBP) could modify the pharmacokinetic property of the doxorubicin (DOX) in Beagle dogs.METHODS: Eight Beagle dogs were treated with LBP capsule (20 mg/kg) or vehicle for 12 continuous days. Plasma concentration of DOX in two groups is monitored after i.v. bolus injection of DOX (1.5 mg/kg) at day 7 and was determined by reverse phase-high performance liquid chromatography with a fluorescence detector. Furthermore, the enzyme activity of cytochrome P450 3A (CYP 3A) in two groups were evaluated.RESULTS: Compared with DOX group, LBP did not modify the pharmacokinetic profiles such as the area under curve and the clearance of DOX in the LPB+DOX group. However, it is proved that LBP could inhibit the activity of CYP 3A , which is a critical metabolizing enzyme of DOX. There is a slight paradox between the inhibition of LBP to CYP 3A and no influence of LBP to pharmacokinetic profiles of intravenous DOX.CONCLUSION: Co-administration of LBP inhibits CYP 3A, the metabolizing enzyme of DOX, but does not affect the pharmacokinetic profiles of intravenous DOX.

Key words: Lycuim barbarum Polysaccharide, cardiotoxicity, herb-drug interaction

中图分类号:

R927.2

余健, 辛艳飞, 顾利强, 高海燕, 张升, 由振强, 温磊, 陈国灿, 陈云祥, 宣尧仙. 枸杞多糖对多柔比星犬药代动力学的影响[J]. 中国临床药理学与治疗学, 2014, 19(3): 246-253.

YU Jian, XIN Yan-fei , GU Li-qiang, GAO Hai-yan, ZHANG Sheng, YOU Zhen-qiang, WEN Lei, CHEN Guo-can, CHEN Yun-xiang, XUAN Yao-xian. Effects of Lycium barbarum Polysaccharide on doxorubicin pharmacokinetics in dogs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 246-253.

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