Effect of Scutellarin on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats.

The study aims to investigate the pharmacodynamics and pharmacokinetics to elucidate the mechanism of enhanced anticoagulant effect of scutellarin and its preparations on warfarin. Evaluation of pharmacodynamic effects is undertaken by measuring coagulation parameters prothrombin time (PT) and activated partial thromboplastin time (APTT). The UHPLC-ESI-MS/MS method is used to determine the plasma concentrations of R/S-warfarin to investigate the influence on the pharmacokinetics. Changes in the plasma protein binding rate of warfarin is studied by ultrafiltration. The results of pharmacodynamics showed that there was no significant difference in PT, international normalized ratio (INR), and APTT between the scutellarin control and the blank control group. Compared to the warfarin control group, scutellarin co-administered with the warfarin group has a significant increase in PT and INR after 8 h, and APTT had no change. The pharmacokinetic results showed that there was an increase in peak concentration (C max) and area under curve (AUC 0-t and AUC 0-∞) and a significant prolongation of half time (t 1/2) and a decrease in apparent clearance (CL/F) of R-warfarin compared with the warfarin control group. Compared with the warfarin group, the protein binding rates were decreased in all doses of scutellarin co-administered with the warfarin groups, respectively. Scutellarin can enhance the anticoagulant effect of warfarin by both inhibition of the R-warfarin metabolism and reduction in the protein binding rate of warfarin.