Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects.
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.
Abdul
Mohi Iqbal Mohammed
MI
Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Jiang
Xuemin
X
Williams
Kenneth M
KM
Day
Richard O
RO
Roufogalis
Basil D
BD
Liauw
Winston S
WS
Xu
Hongmei
H
Matthias
Anita
A
Lehmann
Reginald P
RP
McLachlan
Andrew J
AJ
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
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