title: Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects.
abstract: OBJECTIVE
  This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects.
  
  
  METHODS
  This was an open-label, randomized, three-treatment, cross-over, clinical trial in healthy male subjects (n= 12) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre-treatment with each herbal medicine at recommended doses. Pharmacodynamic (INR, platelet activity) and pharmacokinetic (warfarin enantiomer concentrations) end points were evaluated.
  
  
  RESULTS
  The apparent clearance of (S)-warfarin (90% CI of ratio; 1.01, 1.18) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinically significant change in INR (90% CI of AUC of INR; 0.91, 1.31). Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response. Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre-treatment with the respective herbal medicines.
  
  
  CONCLUSIONS
  Echinacea significantly reduced plasma concentrations of S-warfarin. However, neither echinacea nor policosanol significantly affected warfarin pharmacodynamics, platelet aggregation or baseline clotting status in healthy subjects.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
authors.forename: Mohi Iqbal Mohammed
authors.initials: MI
authors.lastname: Abdul
authors.forename: Xuemin
authors.initials: X
authors.lastname: Jiang
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Williams
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
authors.forename: Basil D
authors.initials: BD
authors.lastname: Roufogalis
authors.forename: Winston S
authors.initials: WS
authors.lastname: Liauw
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Anita
authors.initials: A
authors.lastname: Matthias
authors.forename: Reginald P
authors.initials: RP
authors.lastname: Lehmann
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McLachlan
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D020900:Echinacea; D005233:Fatty Alcohols / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005233:Fatty Alcohols; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; C080710:policosanol; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases