中国中药杂志

2020, v.45(19) 4740-4745

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香丹注射液对大鼠体内华法林抗凝作用的药效学和药代动力学影响
Effects of Xiangdan Injection on pharmacokinetics and pharmacodynamics of warfarin in rats in vivo

姜美婷;张文龙;孙志丹;周洋旭;陈佳玉;刘高峰;
JIANG Mei-ting;ZHANG Wen-long;SUN Zhi-dan;ZHOU Yang-xu;CHEN Jia-yu;LIU Gao-feng;Key Laboratory of University in Heilongjiang Province, Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University;

摘要(Abstract):

研究香丹注射液在大鼠体内对华法林抗凝作用的影响。将大鼠随机分组并给药,于设定的系列时间点取血。测定凝血指标PT(prothrombin time,凝血酶原时间)和APTT(activated partial thromboplastin time,活化部分凝血活酶时间)并计算INR(international normalized ratio,国际标准化比值)。采用UPLC-MS/MS技术测定华法林对映体血药浓度,用DAS 2.0软件计算药代动力学参数,进行统计学分析比较组间差异。单剂量华法林研究结果表明,香丹注射液本身对PT,APTT及INR均无影响,但与华法林联用后,可使PT和INR升高(P<0.01),对APTT无影响;两药联用后,S-华法林的C_(max),AUC_(0-)_t,AUC_(0-∞)升高(P<0.01),t_(1/2)延长(P<0.01),而R-华法林的药动学参数无显著变化。稳态华法林研究结果表明,两药合用后,PT和INR升高(P<0.05),S-华法林血药浓度升高(P<0.01),R-华法林血药浓度无显著变化。研究结果表明,香丹注射液本身对凝血指标无影响,但可通过减慢S-华法林代谢而增强华法林的抗凝作用。
This study is to explore the effect of Xiangdan Injection on anticoagulation of warfarin in rats. Rats were randomly divided into different groups and then administered, subsequently the blood samples were collected at a set series of time points to measure PT(prothrombin time) and APTT(activated partial thromboplastin time) values, and INR(international normalized ratio) value was calculated. The plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS technology, and pharmacokinetic parameters were calculated by DAS 2.0 software. Statistical analysis was performed to compare differences between the groups. Single-dose study of warfarin showed that Xiangdan Injection alone had no effects on PT, APTT and INR, but when co-administrated with warfarin, PT and INR values were increased(P<0.01), while APTT was unaffected; after co-administration of the two drugs, C_(max), AUC_(0-t), and AUC_(0-∞) of S-warfarin increased(P<0.01), and t_(1/2) prolonged(P<0.01), while the pharmacokinetic parameters of R-warfarin were not changed significantly. Steady-state study of warfarin showed that after co-administration of the two drugs, the PT and INR values increased(P<0.05), and the plasma concentration of S-warfarin increased(P<0.01), while the plasma concentration of R-warfarin was not changed significantly. The results suggest that Xiangdan Injection itself has no effect on coagulation index, but can enhance the anticoagulant effect of warfarin by slowing metabolism of S-warfarin.

关键词(KeyWords): 香丹注射液;华法林;抗凝作用;药物相互作用;药效学;药代动力学
Xiangdan Injection;warfarin;anticoagulant effect;drug interactions;pharmacodynamics;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81173659)

作者(Author): 姜美婷;张文龙;孙志丹;周洋旭;陈佳玉;刘高峰;
JIANG Mei-ting;ZHANG Wen-long;SUN Zhi-dan;ZHOU Yang-xu;CHEN Jia-yu;LIU Gao-feng;Key Laboratory of University in Heilongjiang Province, Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University;

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