Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats

1. Safflower injection (SI) is extracted from Chinese herbal medicine safflower that comprises many active components. Warfarin is a common anticoagulant and has exhibited drug interactions with several herbal products. This study aimed to investigate the effects of SI on pharmacodynamics and pharmacokinetics of warfarin in rats. 2. Wistar rats were randomly divided into blank control group, SI group, warfarin control group and SI+warfarin group, respectively. In SI and SI+warfarin groups, rats were injected with SI (1.6 mL/kg/d, i.p.) for 14days. Warfarin (0.2 mg/kg) was given orally on the eighth day. Saline was given as control. The blood samples were collected at various time points. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. UPLC-MS/MS was used to determine the plasma concentrations of S(R)-warfarin, and the pharmacokinetic parameters were calculated. 3. PT, APTT in SI and SI+warfarin rats increased significantly compared with corresponding control rats. The pharmacokinetic parameters including C-max, t(1/2), AUC(0-t) and AUC(0-infinity) of S-warfarin and R-warfarin in SI+warfarin rats were higher than those in warfarin control rats. 4. These findings suggest that SI significantly increases the anticoagulant effect of warfarin by affecting its pharmacodynamic and pharmacokinetic parameters.