The Effect Of Danshen On Steady State Warfarin Pharmacodynamics And Pharmacokinetics In Rats

Danshen (salvia miltiorrhiza) is a popular Chinese herb medicine that has been used for thousands of years for the treatment of various cardiovascular diseases. Warfarin is an anticoagulant widely used in the treatment and prophylaxis of various thromboembolic disorders. Clinically significant interactions between warfarin and other drugs are known to occur.The objective of this study was to determine if Danshen injection has an effect on steady-state warfarin pharmacodynamics and pharmacokinetics in rats.A stratified randomization,multiple dose,between group comparative parallel study design was used. Three groups (Danshen group;warfarin group;Danshen plus warfarin group ) were compared. Prothrombin time (PT) and warfarin plasma concentration (Cp) were measured by using chemical analyzer and HPLC respectively. Danshen (salvia miltiorrhiza injection) was administered in a dose of 5g/kg IP twice daily for 10 days and warfarin was given in a dose of 0.2mg/kg/day orally for 10days. Blood samples for PT and Cp measurement were collected on days 1 (prior to drug administration),6 and 10 .Within group Danshen comparison of the PT and INR for the three measurement days (days 1,6,10) suggested that Danshen itself had no significant effect on PT and INR (P >0.05). Between groups analysis suggested no significant difference in the mean PT and INR values between groups on day 1 (P> 0.05). On day 6 and 10,there was significant difference in PT and INR (P < 0.005) between the Danshen group and warfarin group,Danshen+Warfrin group;When Danshen was added to warfarin,there was an increase in PT and INR when compared to warfarin group,this difference in PT did not reach statistical significance (P = 0.201),but it may have a very important clinical significance. The difference in INR did reach statistical significance (P < 0.005). There was an increase in the mean warfarin serum concentration of day 6 and 10 and other pharmacokinetics parameters when Danshen was added to warfarin when compared to warfarin group. Both of them reach statistical significance ( P < 0.005 ).It appears that Danshen can significantly affect both the pharmacokinetics and pharmacodynamics of warfarin by increasing warfarin Cp and prolonging the PT. This interaction has the potential to cause serious bleeding episodes.