Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.

Systematic evidence regarding herb-drug interactions is lacking. This study investigated herb-drug interactions with warfarin. S-warfarin concentration and response (prothrombin complex activity) data from healthy subjects (n = 24) who received a single warfarin dose (25 mg) and either St John's wort, Asian ginseng, Ginkgo biloba, or ginger were analyzed using a population pharmacokinetic-pharmacodynamic modeling approach. The ratio of S-warfarin apparent clearance (CL/F) compared to control was 1.39 +/- 0.06 and 1.14 +/- 0.04 after St John's wort and Asian ginseng pretreatment, respectively. Other pharmacokinetic and pharmacodynamic parameters were unaffected. Coadministration of St John's wort significantly increased S-warfarin CL/F, whereas treatment with Asian ginseng produced only a moderate increase in CL/F. Ginkgo and ginger did not affect the pharmacokinetics of warfarin in healthy subjects. None of the herbs studied had a direct effect on warfarin pharmacodynamics. Studies in anticoagulated patients are warranted to assess the clinical significance of these herb-drug interactions.