刺五加注射液对大鼠华法林抗凝作用的影响.doc

刺五加注射液对大鼠华法林抗凝作用的影响 李婷婷，刘 艳，冯立影，梁晓玲，赵海峰，刘高峰* [摘 要] 目的 研究刺五加注射液对大鼠华法林抗凝作用的药效学和药动学影响，为临床合理用药提供参考。方法 将Wistar雄性大鼠随机分成空白对照组A组、给药组B组、华法林对照组C组、华法林-联合给药组D组，4组大鼠连续腹腔注射生理盐水或注射液15mL/kg）14天。第8天，A、B两组灌胃给予相同剂量的生理盐水C、D两组灌胃给予华法林0.2mg/kg），并于设定的一系列时间点取血。用血凝分析仪测定凝血酶原时间（PT）、活化部分凝血活酶时间（APTT），并计算国际标准化比值（INR）。用UPLC-MS/MS法联合手性色谱柱技术测定血浆中华法林（包括S-型和R-型）浓度，用DAS2.0软件计算药代动力学参数PT、APTT及INR与华法林对照组比较，刺五加注射液，华法林S-型和R-型）的药动学参数CmaxAUC0-t和AUC0-∞等显著升高（P0.05或P0.01），药效学参数PT及INR显著增加（P0.05或P0.01）。结论 刺五加注射液可减慢华法林（包括S-型和R-型）的代谢，使华法林抗凝作用增强。提示临床用药时应尽量避免两药联合应用，以避免出血风险，如必须联用，应密切监测。 [关键词] 华法林；刺五加注射液；抗凝作用；药物相互作用 Influence of Ciwujia Injection on Anticoagulant Effect of Warfarin in Rats LI Ting-ting, LIU Yan, FENG Li-ying, LIANG Xiao-ling, ZHAO Hai-feng, LIU Gao-feng* (Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Key Laboratory of University in Heilongjiang Province, Harbin 150086, Heilongjiang, China) [ABSTRACT] Objective To study effects of Ciwujia injection on the pharmacodynamics and pharmacokinetics of warfarin in rats, and to provide reference for rational drug use of combination therapy. Methods Wistar rats were randomly divided into four groups, blank control group (group A) , Ciwujia injection group (group B) , warfarin control group (group C) , warfarin combined Ciwujia injection group (group D) , eight in each group. The four groups of rats were administered physiological saline or Ciwujia injection (15mL/kg) by caudal vein for 14 consecutive days. On the eighth day, A、B groups were orally administered with same dose of physiological saline, and C、D groups of rats were orally administered with warfarin solution (0.2mg/kg) . The blood samples were collected from the caudal veins at different times. The prothrombintime (PT) and activated partial thromboplastin time (APTT) of the blood samples were determined by Coagulation analyzer, and the blood concentrations of S-warfarin and R-warfarin were determined by UPLC-MS/MS. Pharmacokinetic parameters were calcul