TY - JOUR
T1 - Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects
AU - Mohammed Abdul, Mohi Iqbal
AU - Jiang, Xuemin
AU - Williams, Kenneth M.
AU - Day, Richard O.
AU - Roufogalis, Basil D.
AU - Liauw, Winston S.
AU - Xu, Hongmei
AU - Matthias, Anita
AU - Lehmann, Reginald P.
AU - McLachlan, Andrew J.
PY - 2010
Y1 - 2010
N2 - Aims: 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. CONCLUSION 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.
AB - Aims: 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. CONCLUSION 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.
KW - drug, herb interactions
KW - echinacea (plants)
KW - pharmacokinetics
KW - policosanol
KW - warfarin
UR - http://handle.uws.edu.au:8081/1959.7/uws:31647
U2 - 10.1111/j.1365-2125.2010.03620.x
DO - 10.1111/j.1365-2125.2010.03620.x
M3 - Article
SN - 0306-5251
VL - 69
SP - 508
EP - 515
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 5
ER -