Mei-Ting Jiang, Wen-Long Zhang, Zhi-Dan Sun, Yang-Xu Zhou, Jia-Yu Chen, Gao-Feng Liu
Key Laboratory of University in Heilongjiang Province, Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
Zhongguo Zhong Yao Za Zhi. 2020 Oct;45(19):4740-4745. doi: 10.19540/j.cnki.cjcmm.20200618.202.
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.
本研究旨在探讨香丹注射液对大鼠体内华法林抗凝作用的影响。将大鼠随机分为不同组并给药，随后在一系列设定的时间点采集血样，以测定凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）值，并计算国际标准化比值（INR）。采用超高效液相色谱-串联质谱技术测定华法林对映体的血浆浓度，并用DAS 2.0软件计算药代动力学参数。进行统计分析以比较各组之间的差异。华法林单剂量研究表明，单独使用香丹注射液对PT、APTT和INR无影响，但与华法林合用时，PT和INR值升高（P<0.01），而APTT不受影响；两种药物合用时，S-华法林的Cmax、AUC0-t和AUC0-∞升高（P<0.01），t1/2延长（P<0.01），而R-华法林的药代动力学参数无显著变化。华法林稳态研究表明，两种药物合用时，PT和INR值升高（P<0.05），S-华法林的血浆浓度升高（P<0.01），而R-华法林的血浆浓度无显著变化。结果表明，香丹注射液本身对凝血指标无影响，但可通过减缓S-华法林的代谢来增强华法林的抗凝作用。
