Abstract：
This study investigated whether Safflower Yellow for injection (SYI) would affect the anticoagulation of warfarin in rats.Wistar male rats were divided into six groups randomly and administered with SYI (9 mg/kg, intraperitoneal injection) in single-dose and steady-dose warfarin (0.2 mg/kg, oral gavage), respectively. The pharmacodynamic parameters of PT and APTT were measured by a coagulation analyser. R/S-warfarin concentration was measured by UHPLC-MS/MS, and pharmacokinetic parameters calculated using DAS 2.0 software.The single-dose study demonstrated that SYI, alone or co-administered with warfarin, could significantly increase PT, INR, and APTT values (p < 0.01). R-warfarin Cmax, AUC, and t1/2 values increased by 9.25% (p > 0.05), 25.96% (p < 0.01), and 26.17% (p < 0.01), respectively, whereas the CL/F value reduced by 22.22% (p < 0.01) in the presence of SYI. Meanwhile, S-warfarin Cmax, AUC, and t1/2 values increased by 37.41%, 32.11%, and 31.73% (all p < 0.01), respectively, whereas the CL/F value reduced by 33.33% (p < 0.01). The steady-dose study showed that PT, INR, APTT, and the concentrations of R/S-warfarin increased significantly when SYI was co-administered with warfarin (p < 0.01).SYI can enhance warfarin\'s anticoagulation intensity and decelerate its metabolism in rats.
摘要：
本研究调查了注射用红花黄色素（SYI）是否会影响华法林在大鼠体内的抗凝作用。Wistar雄性大鼠随机分为6组,给予SYI(9mg/kg,腹膜内注射）单剂量和稳定剂量华法林（0.2mg/kg，分别口服管饲法）。通过凝血分析仪测量PT和APTT的药效学参数。通过UHPLC-MS/MS测定R/S-华法林浓度,并使用DAS2.0软件计算药代动力学参数。单剂量研究表明，SYI，单独或与华法林联合给药，可以显着增加PT，INR,和APTT值(P<0.01)。R-华法林Cmax,AUC,t1/2值增加了9.25%(P>0.05)，25.96%(P<0.01),分别为26.17%(P<0.01),而在SYI存在下，CL/F值降低了22.22％（P<0.01）。同时,S-华法林Cmax,AUC,t1/2值增加了37.41%，32.11%,分别为31.73%(P均<0.01),CL/F值降低了33.33%(P<0.01)。稳定剂量研究表明，PT，INR,APTT,SYI与华法林联合给药时，R/S-华法林的浓度显着增加（P<0.01）。SYI可以增强华法林的抗凝强度，减缓其在大鼠体内的代谢。
