THE EFFECTS OF DANSHEN (SALVIA-MILTIORRHIZA) ON WARFARIN PHARMACODYNAMICS AND PHARMACOKINETICS OF WARFARIN ENANTIOMERS IN RATS

The effects of Danshen (Salvia miltiorrhiza), a popular traditional Ch inese medicinal herb on the pharmacokinetics and pharmacodynamics of R - and S-warfarin stereoisomers were studied in rats. After a single or al dose of racemic warfarin (2 mg kg(-1)), treatment with oral Danshen extract (5 g kg(-1) twice daily) for 3 days significantly altered the overall pharmacokinetics of both R- and S-warfarin and increased the plasma concentrations of both enantiomers over a period of 24 h and th e prothrombin time over 2 days. At steady-slate levels of racemic warf arin (0.2 mg kg day(-1) for 5 days) the 3-day treatment of Danshen ext ract (5 g kg(-1), twice daily) not only prolonged the prothrombin time but also increased the steady-state plasma concentrations of R- and S -warfarin.The results indicate that Danshen extracts can increase the absorption rate constant, area under plasma concentration-time curves, maximum concentrations and elimination half-lives, but decreases the clearances and apparent volume of distribution of both R- and S-warfar in. The pharmacokinetic and pharmacodynamic interactions of warfarin d uring co-treatment with Danshen extract observed in this study indicat e an explanation for the clinically observed incidents of exaggerated warfarin adverse effects when traditional Chinese medicinal herbs or h erbal products such as Danshen and Danggui (observed in a previous stu dy) were co-administered.