中药注射剂对华法林抗凝作用的影响及相关机制的研究进展
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摘要
目前研究结果显示,有些中药注射剂,如丹参注射液、刺五加注射液、注射用血栓通、丹红注射液、疏血通注射液、红花注射液可使华法林的抗凝作用增强。相关作用机制包括药动学相互作用,如影响华法林的血浆蛋白结合率,抑制或诱导华法林代谢相关的细胞色素P_(450)酶,以及药效学影响。有些中药注射剂与华法林联用有出血风险,但亦有临床研究显示治疗某些血栓栓塞性疾病时,可利用两者协同抗凝作用而对治疗产生有益的影响,但尚缺乏循证研究和评价。因此,在临床用药过程中,应关注中药注射剂对华法林抗凝作用可能产生的影响,密切监测患者国际标准化比值,或适当调整华法林剂量,或避免有相互作用的药物联合应用,以保障患者用药安全。
Up to now, the results showed that some traditional Chinese medicine injections such as Salvia miltiorrhiza injection, Acanthopanax injection, Xueshuantong injection, Danhong injection, Shuxuetong injection and Safflower injection could enhance the anticoagulant effect of warfarin. The mechanisms include pharmacokinetic interactions such as influence on plasma protein binding of warfarin, inhibiting or inducing activities of warfarin-related cytochrome P_(450) metabolic enzymes, and pharmacodynamic influence. Some traditional Chinese medicine injections have a bleeding risk in combination with warfarin. Clinical studies have also shown that the use of synergistic anticoagulant effects in the treatment of certain thromboembolic diseases can have a beneficial effect on treatment, but there is still no evidence-based research and evaluation. Therefore, attention should be paid to the possible influence of traditional Chinese medicine injections on warfarin anticoagulation in clinic, and INR needs to be monitored closely for the patients, or adjust warfarin dosage appropriately, or avoid the combined use of the two kinds of drugs with mutual effects, so as to ensure safety of patient.
Up to now, the results showed that some traditional Chinese medicine injections such as Salvia miltiorrhiza injection, Acanthopanax injection, Xueshuantong injection, Danhong injection, Shuxuetong injection and Safflower injection could enhance the anticoagulant effect of warfarin. The mechanisms include pharmacokinetic interactions such as influence on plasma protein binding of warfarin, inhibiting or inducing activities of warfarin-related cytochrome P_(450) metabolic enzymes, and pharmacodynamic influence. Some traditional Chinese medicine injections have a bleeding risk in combination with warfarin. Clinical studies have also shown that the use of synergistic anticoagulant effects in the treatment of certain thromboembolic diseases can have a beneficial effect on treatment, but there is still no evidence-based research and evaluation. Therefore, attention should be paid to the possible influence of traditional Chinese medicine injections on warfarin anticoagulation in clinic, and INR needs to be monitored closely for the patients, or adjust warfarin dosage appropriately, or avoid the combined use of the two kinds of drugs with mutual effects, so as to ensure safety of patient.
引文
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[32] 秦梦楠,刘蕊,刘高峰,等.灯盏花素注射液对大鼠体外肝微粒体细胞色素P450酶活性的影响[J].中国药师,2012,15(2):147-150.
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[34] 韩永龙,余奇,孟祥乐,等.灯盏细辛注射液对大鼠肝微粒体CYP3A的抑制作用[J].中国临床药理学与治疗学,2009,14(8):891-895.
[35] 韩永龙,孟祥乐,李丹,等.清开灵注射剂等5种中药注射剂对对大鼠肝微粒体CYP3A的体外抑制作用[J].中国中药杂志,2011,36(4):492-495.
[36] XIA C H,SUN J H,WANG G J,el al.Herbdrug interac-tion:in vivo and in vitro effect of Shenmai injection,a herbal preparation,on the metabolic activities of hepatic cyochrome P450 3A1/2,2C6,1A2 and 2E1 in rats [J].Planta Med,2010,76(3):245-250.
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[38] 叶林虎,贺梅,常琪,等.喜炎平注射液对人肝微粒体P450酶活性的影响[J].中国临床药理学杂志,2014,30(9):797-799.
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[2] 肖幸,周仑,高翔.41例服用华法林老年患者国际标准化比值异常变化的药物因素[J].医药导报,2018,37(1):107-109.
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[4] 王晓蕊,毛静远.中药影响华法林抗凝作用的研究进展[J].中西医结合心脑血管病杂志,2016,14(20):2379-2383.
[5] 杜娟.65例常用中药注射剂不良反应原因分析及临床对策[J].海峡药学,2012,24(10):265-266.
[6] 周庆,伍三兰,韩勇.华法林导致皮下严重出血的药学监护[J].医药导报,2016,35(4):427-428.
[7] 耿强,郭丹杰.65岁以上老年患者口服华法林抗凝的安全性探讨[J].中西医结合心脑血病杂志,2009,7(7):834-835.
[8] HYLEK E M,EVANS-MOLINA C,SHEA C,et al.Major hemorrhage and tolerability of wafarin in first year of therapy among elderly patients with atrial fibrillation[J].Circulation,2007,115(21):2689-2696.
[9] 李乐,程欣,王晶晶.中药注射剂与华法林药物相互作用的研究进展[J].中国老年保健医学,2016,14(3):59-61.
[10] 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.
[11] 张德隆,王洪志.一例华法林与注射用丹参多酚酸盐合用致眼结膜出血的病例分析[J].首都食品与医药,2018,25(15):66.
[12] 谢红娟,付海英,朱彩凤,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):36-40.
[13] 李婷婷,刘艳,冯立影,等.刺五加注射液对大鼠华法林抗凝作用的影响[J].实用药物与临床,2015,18(11):1280-1283.
[14] 杜立峰,郑海燕,王鹏.注射用血栓通对华法林在大鼠体内药效学和药动学的影响[C].基层医疗机构从业人员科技论文写作培训会议论文集,2016.
[15] 冯立影,梁晓玲,李婷婷,等.丹红注射液对大鼠体内华法林抗凝作用的影响[J].中国药师,2016,19(1):1-4.
[16] 赵海峰,孙佳慧,刘爽,等.疏血通注射液对大鼠体内华法林抗凝作用的影响[J].中国中药杂志,2017,42(5):982-988.
[17] LIU Y,LIU S,SHI Y,et al.Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats [J].Xenobiotic,2018,48(8):818-823.
[18] SUN J,LU Y,LI Y,et al.Influence of shenxiong glucose injection on the activities of six CYP isozymes and metabolism of warfarin in rats assessed using probe cocktail and pharmacokinetic approaches[J].Molecules,2017,22(11):1994.
[19] 谭毓治,伍爱婵,谭丙炎,等.小檗碱竞争血浆蛋白结合部位所致药物相互作用的研究[J].中国药理学通报,2002,28(5):576-578.
[20] 卜明华,郑咏秋,张颖,等.参麦注射液和注射用血塞通对大鼠肝脏及肠道药物代谢酶P450的影响[J].中国临床药理学杂志,2012,28(1):49-51.
[21] 于初楚,胡冰,褚杨,等.注射用益气复脉(冻干)对大鼠肝微粒体CYP1A2,CYP3A4活性的影响研究[J].中国中药杂志,2011,10(36):1378-1381.
[22] 石杰,陈安进,张芳,等.血塞通及川芎嗪对细胞色素P450不同亚型代谢酶影响的研究[J].中国中西医结合急救杂志,2008,15(6):342-345.
[23] LIU R,QIN M N,HANG P Z,et al.Effects of Panax Notoginseng saponins on the activities of CYP1A2,CYP2C9,CYP2D6 and CYP3A4 in rats in vivo[J].Phytother Res,2012,26(8):1113-1118.
[24] 卫常松.金纳多对大鼠肝脏细胞色素P450酶活性的影响[J].山东医药,2008,40(48):6.
[25] 张咏莉.黄芪颗粒和黄芪注射液对CYP1A2、CYP2D、CTP2C亚酶活性影响的实验研究[J].中国药理学通报,2013,29(4):512-519.
[26] YU Y,LIU Y,LI Q,et al.Effects of Guanxinning injection on rat cytochrome P450 isoforms activities in vivo and in vitro[J].Xenobiotic,2015,45(6):481-487.
[27] 简瞰昱.五种滇产中药主要药效成分及灯盏花素注射液对大鼠CYP1A2体内外抑制活性研究[D].昆明:昆明医学院,2011:21-34.
[28] 赵文婷,张波,李湘晖,等.疏血通注射液对大鼠细胞色素P450酶6种亚型活性的影响[J].中药新药与临床药理,2012,23(4):445-449.
[29] 余小翠,黄丽军,刘高峰,等.丹红注射液对大鼠肝微粒体5种CYP亚型酶活性的影响[J].医药导报,2012,31(3):277-281.
[30] 陈为烤.脉络宁注射液的代谢性药物相互作用研究[D].南京:南京中医药大学,2009:31-49.
[31] 叶林虎.醒脑静注射液对人肝微粒体P450酶5种亚型体外抑制作用[J].中国新药与临床杂志,2016,35(7):512-517.
[32] 秦梦楠,刘蕊,刘高峰,等.灯盏花素注射液对大鼠体外肝微粒体细胞色素P450酶活性的影响[J].中国药师,2012,15(2):147-150.
[33] 许黎君,居文政,陈为烤,等.灯盏细辛注射液对小鼠肝微粒体细胞色素P450含量的影响[J].中国临床药理学与治疗学,2008,13(10):1122-1126.
[34] 韩永龙,余奇,孟祥乐,等.灯盏细辛注射液对大鼠肝微粒体CYP3A的抑制作用[J].中国临床药理学与治疗学,2009,14(8):891-895.
[35] 韩永龙,孟祥乐,李丹,等.清开灵注射剂等5种中药注射剂对对大鼠肝微粒体CYP3A的体外抑制作用[J].中国中药杂志,2011,36(4):492-495.
[36] XIA C H,SUN J H,WANG G J,el al.Herbdrug interac-tion:in vivo and in vitro effect of Shenmai injection,a herbal preparation,on the metabolic activities of hepatic cyochrome P450 3A1/2,2C6,1A2 and 2E1 in rats [J].Planta Med,2010,76(3):245-250.
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