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

Abstract

1. This study investigated whether Safflower Yellow for injection (SYI) would affect the anticoagulation of warfarin in rats.

2. 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.

3. 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 C_max, AUC, and t_1/2 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 C_max, AUC, and t_1/2 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).

4. SYI can enhance warfarin’s anticoagulation intensity and decelerate its metabolism in rats.

Keywords:

• Safflower yellow for injection
• warfarin
• anticoagulant effect
• pharmacodynamics
• pharmacokinetics

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author LGF upon reasonable request.

Additional information

Funding

This work was supported by the Key Research and Development Plan of Heilongjiang Province under Grant (No.2022ZX06C12).