Safflower yellow for injection enhances anti-coagulation of warfarin in rats: implications in pharmacodynamics and pharmacokinetics.

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.

Compatibility of Safflower Yellow for Injection with Seven Varieties of Infusions / 中国药师

Objective:To study the stability of safflower yellow for injection respectively mixed with fructose injection,invert sugar injection,invert sugar electrolyte injection,glucose and sodium chloride injection,5% glucose injection,10% glucose injection and 0.9% sodium chloride injection. Methods:The physical appearance,number of particles and pH value were observed at room temper-ature after mixing safflower yellow respectively with above injections for 8 hours at the same concentration as that in clinical use. The content of safflower yellow was determined by high performance liquid chromatography (HPLC). Results: There was no significant difference in appearance,pH or safflower yellow content after the mixing,and the number of insolubility particles met the requirement in Chinese Pharmacopeia (2015 edition).Conclusion:Safflower yellow for injection is stable after dissolved in the 7 varieties of infu-sions in 8h.

Feasibility Study on Bacterial Endotoxin Test for Safflower Yellow for Injection / 中国药师

Objective:To establish a bacterial endotoxin test for safflower yellow for injection to control the drug quality and reduce the incidence of clinical pyrogenic reaction. Methods:The bacterial endotoxin test was carried out according to the methods and guid-ing principles in Chinese Pharmacopoeia ( 2015 edition, volumeⅣ) . A systematic study was carried out to investigate the interference of safflower yellow for injection with limulus reagent and agglutination reaction to bacterial endotoxin in order to detect the non-interfer-ence concentration of bacterial endotoxin. Results: Safflower yellow for injection with the concentration below or equal to 0. 4 mg· ml-1 had no interference with tachypiens amebocyte lysate. Conclusion: Bacterial endotoxin test ( gel method) can be used for the limit test of bacterial endotoxin of safflower yellow for injection, and the results are accurate and reproducible.