Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.
This study, conducted in New South Wales, Australia, 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 [Hypericum perforatum], Asian ginseng (Panax ginseng), Ginkgo biloba or ginger were analysed using a population pharmacokinetic-pharmacodynamic modelling approach. The ratio of S-warfarin apparent clearance (CL/F) compared to the 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. G. biloba 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.