丹参注射液对家兔体内CYP1A2、CYP2D6和CYP3A4活性的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 775-780.

丹参注射液对家兔体内CYP1A2、CYP2D6和CYP3A4活性的影响

刘高峰, 甄立棉, 黄丽军

哈尔滨医科大学附属第二医院药学部,黑龙江省高校重点实验室,哈尔滨 150086,黑龙江

收稿日期:2010-05-18 修回日期:2010-06-23 出版日期:2010-07-26 发布日期:2020-09-15
作者简介:刘高峰,女,博士,主任药师,硕导,研究方向为中药代谢与药物相互作用。Tel: 0451-55969328 E-mail: liugaofengwty@126.com
基金资助:
黑龙江省教育厅科学技术研究项目(11531114)

Effects of Danshen Injection on the activity of rabbit CYP1A2, CYP2D6 and CYP3A4 in vivo

LIU Gao-feng, ZHEN Li-mian, HUANG Li-jun

Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Key Laboratory of University in Heilongjiang Province, Harbin 150086, Heilongjiang, China

Received:2010-05-18 Revised:2010-06-23 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 目的: 用Cocktail探针药物法研究丹参注射液对家兔细胞色素P450亚型酶活性的影响。方法: 将家兔随机分成四组,耳缘静脉注射给予丹参注射液,分低、中、高剂量三个实验组,空白对照组给予生理盐水。用HPLC法测定各组Cocktail探针药物(咖啡因、美托洛尔和氨苯砜)的血药浓度,比较药时曲线及药代动力学参数的变化,评价各组细胞色素P450亚型酶的活性。结果: 丹参注射液低、中、高剂量组CYP2D6的活性与对照组相比降低,具有统计学意义(P＜0.05 或P＜0.01);CYP1A2和CYP3A4的活性与对照组相比差异均无统计学意义。结论: 丹参注射液对家兔CYP2D6有抑制作用,对CYP1A2和CYP3A4的影响不显著。提示临床应用丹参注射液时,应关注其对CYP2D6的抑制作用,避免联合用药引发CYP2D6介导的药物相互作用,促进临床安全合理用药。

关键词: 细胞色素P450(CYP450), 丹参注射液, Cocktail探针药物法

Abstract: AIM: To evaluate the effects of Danshen Injection on rabbit cytochrome P450 (CYP450) activity by Cocktail probe drugs.METHODS: Male rabbits were randomly divided into three test groups and one control group. The test groups were treated with Danshen Injection (i.v.) at three dosages (low, midst and high dosage), and the control group was treated with physiological saline. The plasma concentrations of probe drugs(caffeine,metoprolol and dapsone) were determined by HPLC. Effects of Danshen Injection on CYP450 activity were observed by comparing the concentration-time curves and pharmacokinetic parameters of probe drugs. RESULTS: The three dosages of Danshen Injection inhibited the CYP2D6 activity(P＜0.05, or P＜0.01), but had no effects on the activities of CYP1A2 and CYP3A4. CONCLUSION: Danshen Injection can inhibit CYP2D6 activity in rabbit, but has no effect on CYP1A2 and CYP3A4. When Danshen Injection is used in clinic, attention should be paid to the inhibition effect on CYP2D6 to avoid CYP2D6-mediated drug interaction, and to promote safe and rational drug use.

Key words: Cytochrome P450(CYP450), Danshen Injection, Cocktail probe drugs

中图分类号:

R965.2

刘高峰, 甄立棉, 黄丽军. 丹参注射液对家兔体内CYP1A2、CYP2D6和CYP3A4活性的影响[J]. 中国临床药理学与治疗学, 2010, 15(7): 775-780.

LIU Gao-feng, ZHEN Li-mian, HUANG Li-jun. Effects of Danshen Injection on the activity of rabbit CYP1A2, CYP2D6 and CYP3A4 in vivo[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 775-780.

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