Shi Yuan, Zhang Wenlong, Jiang Meiting, Huang Lijun, Zhou Yangxu, Chen Jiayu, Liu Duo, Liu Gaofeng, Dong Mei
Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Pharmacy, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
Xenobiotica. 2020 Jun;50(6):705-712. doi: 10.1080/00498254.2019.1681034. Epub 2019 Oct 28.
This study was to explore the effects of sulfotanshinone sodium injection (SSI) on the pharmacokinetics and pharmacodynamics of warfarin in rats.The studies of single dose and multiple dose of warfarin were designed to assess the interaction between warfarin and SSI. Rats were divided into different groups randomly and administered with warfarin in the absence or presence of SSI. Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were detected by blood coagulation analyzer, and international normalized ratio (INR) values were calculated. Plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS method, pharmacokinetic parameters were calculated.The single-dose study demonstrated that the repeated doses of SSI alone had no effect on PT, APTT and INR values, but had a significant effect on PT and INR values produced by a single dose of warfarin, APTT values were unaffected. The , of R-warfarin and S-warfarin were reduced, were shortened. The multiple-dose study showed that PT, APTT, INR values, and the and of R-warfarin and S-warfarin decreased significantly after administration of SSI.The finding implied that SSI could accelerate warfarin metabolism and weaken its anticoagulation. However, human SSI-warfarin interaction studies need to be conducted to confirm this finding.
本研究旨在探讨丹参磺酸钠注射液（SSI）对大鼠体内华法林药代动力学和药效学的影响。设计华法林单剂量和多剂量研究以评估华法林与SSI之间的相互作用。将大鼠随机分为不同组，在不存在或存在SSI的情况下给予华法林。用凝血分析仪检测凝血酶原时间（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）值。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定血浆中华法林对映体的浓度，计算药代动力学参数。单剂量研究表明，单独重复给予SSI对PT、APTT和INR值无影响，但对单剂量华法林产生的PT和INR值有显著影响，APTT值未受影响。R-华法林和S-华法林的 降低， 缩短。多剂量研究表明，给予SSI后，PT、APTT、INR值以及R-华法林和S-华法林的 和 显著降低。该发现表明SSI可加速华法林代谢并减弱其抗凝作用。然而，需要进行人体SSI-华法林相互作用研究以证实这一发现。
