中药对华法林作用的影响及机制概述

摘要/Abstract

摘要： 华法林是临床常用的一种香豆素类口服抗凝药,具有蛋白结合率高、依赖细胞色素P450酶代谢及治疗窗窄等特点,易与其他药物发生相互作用,造成患者出血风险增加或抗凝治疗不足等严重后果。中药在治疗心脑血管疾病等方面具有独特的优势,临床应用广泛,与华法林合用的机会较多。本文根据已有的实验研究和临床案例报道,分别对单味中药及中药复方制剂对华法林抗凝作用的影响及相关机制进行了综述和探讨,以期为临床合理用药和相关研究提供参考。

关键词: 中药, 华法林, 细胞色素P450, 抗凝, 药物相互作用

Abstract: Warfarin is an oral coumarin anticoagulants which has been commonly used in clinic for anticoagulant therapy, with high protein binding rate, relying on the cytochrome P450 enzyme metabolism, and with narrow therapeutic window, etc.. It easily interacts with other drugs, resulting in serious consequences, such as increased bleeding risk or inadequate anticoagulant therapy. Traditional Chinese medicine has been widely used in the treatment of cardiovascular diseases with unique advantages, and has more opportunities to be coadministered with warfarin.According to the experimental and clinical researches that have been published, the effects and the mechanisms of single traditional Chinese herbs and compound Chinese traditional medicine preparations on warfarin were reviewed and discussed in this paper, in order to provide reference for clinical rational drug use and related researches.

Key words: Traditional Chinese Medicine, warfarin, cytochrome p450, anticoagulant, drug interactions

中图分类号:

殷硕, 于月, 郭兴蕾, 刘高峰. 中药对华法林作用的影响及机制概述[J]. 中国临床药理学与治疗学, 2015, 20(3): 327-334.

YIN Shuo, YU Yue, GUO Xing-lei, LIU Gao-feng. Effects of traditional Chinese medicine on the role of warfarin and the mechanisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(3): 327-334.

参考文献

[1] Harder S, Thürmann P. Clinically important drug interactions with anticoagulants.An update[J]. Clin Pharmacokinet, 1996, 30(6): 416-444.
[2] Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin[J]. Pharmacol Ther, 1997, 73(1):67-74.
[3] Lo AC, Chan K, Yeung JH, et al. The effects of Danshen(Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats[J]. Eur J Drug Metab Pharmacokinet, 1992, 17(4):257-262.
[4] Chan K, Lo AC, Yeung JH, et al. The effects of Danshen(Salvia miltiorrhiza) on pharmacodynamics and pharmacokinetics of warfarin in rats[J]. J Pharm Pharmacol, 1995, 47(5):402-406.
[5] 颜青,蒋锦琪. 丹参片对华法令抗凝作用影响[J]. 中成药,2008,30(1):19-21.
[6] 谢红娟,付海英,Sands CD,等. 丹参注射液对大鼠体内稳态华法林药动学和药效学参数的影响[J]. 医药导报,2009,28(1):36-39.
[7] Liu J, Wang X, Cai Z, et al. Effect of tanshinone ⅡA on the noncovalent interaction between warfarin and human serum albumin studied by electrospray ionization mass spectrometry[J]. J Am Soc Mass Spectrom, 2008, 19(10): 1568-1575.
[8] Tam LS, Chan TY, Leung WK,et al.Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil[J].Aust NZ J Med, 1995, 25:258.
[9] Izzat MB, Yim AP, EI-Zufari.A taste of Chinese medicine[J]. Ann Thorac Surg, l998, 66(3):936-941.
[10]Qiu F, Zhang R, Sun J, et al. Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes[J]. Drug Metab Dispos, 2008, 36(7):1308-1314.
[11]Wang X, Lee WY, Or PM, et al. Pharmacokinetic interaction studies of tanshinones with tolbutamide, a model CYP2C11 probe substrate, using liver microsomes, primary hepatocytes and in vivo in the rat[J]. Phytomedicine, 2010, 17(3/4):203-211.
[12]Zhou Y, Zeng R. Effects of Ginkgo biloba extract on anticoagulation and blood drug level of warfarin in healthy volunteers[J]. Zhongguo Zhong Yao Za Zhi, 2011, 36(16): 2290-2293.
[13]Engelsen J, Nielsen JD, Hansen KF.Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment: a randomized, double-blind, placebo-controlled cross-over trial[J]. Ugeskr Laeger, 2003, 165(18):1868-1871.
[14]王尚昆. 银杏叶片对华法林抗凝药效影响的临床研究[J]. 中国医疗前沿,2013,8(16):13-14.
[15]毕绮丽,古淑仪,吴苑珊. 银杏叶注射剂对华法林抗凝效果的影响[J]. 现代医院,2011,11(3):6-7.
[16]Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage[J]. Neurology, 1998, 50(6): 1933-1934.
[17]唐关敏. 银杏叶及蒺藜制剂对华法林抗凝作用的影响[J]. 浙江医学,2007,29(8):868-869.
[18]He N, Edeki T. The Inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes[J]. Am J Ther, 2004, 11(3):206-212.
[19]Greenblatt DJ, von Moltke LL, Luo Y, et al. Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P4502C9 substrate[J]. J Clin Pharmacol, 2006, 46(2): 214-221.
[20]Taki Y, Yokotani K, Yamada S, et al. Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice[J]. Phytomedicine, 2012, 19(2):177-182.
[21]周晶.草药与西药的相互作用[J]. 天津药学,2002,14(5): 76-77.
[22]沈连忠,崔艳英,王淑仙,等.银杏叶提取物血液流变学研究[J].中国中药杂志,1998,23(10):622-623.
[23]Lo AC, Chan K, Yeung JH, et al. Danggui(Angelica Sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits[J]. Drug Metab Pharmcaokinet, 1995, 20(1):55-60.
[24]Page RL, Lawrence JD. Potentiation of warfarin by Dong quai[J]. Pharmacotherapy,l999,19(7):870-876.
[25]张彦丽,王景红,桂玥,等. 华法林与中草药的相互作用[J]. 中国药物警戒,2011,8(1):41-45.
[26]杨铁虹,商澎,梅其炳. 当归多糖硫酸酯对凝血和血小板聚集的作用[J]. 中草药,2002,33(11):1010-1013.
[27]李敏,孙虹,李琰,等. 不同产地当归对血小板聚集及凝血时间活性的比较[J]. 中国中医基础医学杂志, 2003,9(2):47-50.
[28]张宇. 华法林联用红花水煎剂致泌尿系出血1例分析[J]. 长春中医药大学学报,2012,28(3):466.
[29]赵金明,秦文艳,齐越,等. 红花黄色素抗凝血作用及对血小板聚集影响的研究[J].实验动物科学,2009,26(6):30-32.
[30]徐露,董志. 注射用羟基红花黄色素A对家兔血小板聚集、超微结构及血小板活化因子诱导后富血小板血浆中GMP-140含量的影响[J].中国临床药理学与治疗学,2012,17(3):269-273.
[31]周群,汪晓云,代莉,等.红花注射液对冠心病患者血小板、凝血及纤溶功能的影响[J]. 中国综合临床,2002,18(10):888-889.
[32]Lam AY, Elmer GW, Mohutsky MA. Possible interaction between warfarin and Lycium barbarum L[J]. Ann Pharmacother, 2001, 35(10):1199-1201.
[33]Leung H, Hung A, Hui AC, et al. Warfarin overdose due to the possible effects of Lycium barbarum L[J]. Food Chem Toxicol, 2008, 46:1860-1862.
[34]Rivera CA, Ferro CL, Gerber BS, et al. Probable Interaction Between Lycium barbarum (Goji) and Warfarin[J]. Pharmacotherapy, 2012, 32(3):e50-e53.
[35]Joss JD, Leblond RF. Potentiation of warfarin anticoagulation associated with topical methyl salicylate[J]. The annuals of Pharmacotherapy, 2000, 34(6):729-733.
[36]吉腾飞,沙也夫,张宏志,等. 鹿蹄草属植物化学成分研究进展[J].中草药,1999,30(2):154-155.
[37]李绪玲. 鹿衔草的药理作用及临床应用研究进展[J]. 中国医学创新,2010,7(12):185-186.
[38]彭延古,雷田香,李路丹,等. 全蝎提取液对家兔实验性动脉血栓的影响[J]. 微循环学杂志,2006,16(4):59-60.
[39]李嫦玲,周知午. 全蝎粉对华法林在人体内血药浓度和抗凝血功能的影响[J]. 湖南中医杂志,2011,27(3):136-137.
[40]朱灵,杨春旭,黎渊弘. 蝎龙液浸膏体内外对动物凝血功能及血栓形成的影响[J]. 现代中药研究与实践,2008,22(4): 22-47.
[41]Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin's effect in healthy patients:a randomized, controlled trial[J]. Ann Intern Med, 2004, 141(1):23-27.
[42]Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng[J]. Am J Health Syst Pharm, 1997, 54(6): 692-693.
[43]Lee SH, Ahn YM, Ahn SY, et al. Interaction between warfarin and Panax ginseng in ischemic stroke patients[J]. J Altern Complement Med, 2008, 14(6):715-721.
[44]Lee YH, Lee BK, Choi YJ, et al. Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement[J]. Int J Cardiol, 2010, 145(2):275-276.
[45]Thomson Micromedex Healthcare Series [C/P]. Colorado(USA): The Thomson Corporation: 2007.
[46]Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects[J]. Br J Clin Pharmacol, 2004, 57(5):592-599.
[47]Yue QY, Bergquist C, Gerden B. Safety of St John'S wort (Hypericum perforatum)[J].Lancet, 2000, 355(9203): 575-577.
[48]吴敏,王霞,许平. 贯叶连翘的研究进展[J]. 中成药,2004,26(9):760-763.
[49]沈燕,罗启剑. 贯叶连翘药物相互作用研究进展[J]. 药学服务与研究,2008,8(1):63-65.
[50]易丹,罗晓波,周于禄,等. 复方丹参滴丸对华法林在人体内药动学和药效学的影响[J]. 中国药物警戒,2013,10(2):65-67.
[51]刘燕,李振洲,曹燕滔,等. 疏血通注射液和华法林联用致国际标准化比率升高[J]. 药物不良反应杂志,2007,9(3): 217-218.
[52]陈华友,黄静,蒋芝君,等. 抗凝良药水蛭素的研究进展[J]. 生物学通报,2003,38(3):3-5.
[53]董强,乔健,史郎峰,等. 蚓激酶胶囊治疗脑梗死患者的疗效和安全性[J]. 中国新药杂志,2004,13(3):257-260.
[54]项海燕,唐燕华. 新癀片对华法林抗凝治疗的影响[J]. 中国老年学杂志,2013,33(13):3189-3190.
[55]Wong AL, Chan TY. Interaction between warfarin and the herbal product guilinggao[J]. Ann Pharmacother, 2003, 37(6):836-838.
[56]Su Q, Li Y. Interaction between warfarin and the herbal product Shengmai-yin: a case report of intracerebral hematoma[J]. Yonsei Med J, 2010, 51(5):793-796.