title: Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, the University of Sydney, NSW 2006, Australia.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Jiang
authors.forename: Elaine Y L
authors.initials: EY
authors.lastname: Blair
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McLachlan
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020939:Zingiber officinale; D020441:Ginkgo biloba; D006262:Health; D041743:Herb-Drug Interactions / Q000502:physiology*; D029001:Herbal Medicine; D006801:Humans; D020902:Hypericum; D008297:Male; D008954:Models, Biological; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D010936:Plant Extracts; D014859:Warfarin