Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects

Abstract

AimThe aim of this study was to investigate the effect of two common herbal medicines, ginkgo and ginger, on the pharmacokinetics and pharmacodynamics of warfarin and the independent effect of these herbs on clotting status. MethodsThis was an open label, three-way crossover randomized study in 12 healthy male subjects, who received a single 25 mg dose of warfarin alone or after 7 days pretreatment with recommended doses of ginkgo or ginger from herbal medicine products of known quality. Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose. Platelet aggregation, international normalized ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured. Statistical comparisons were made using ANOVA and the 90% confidence intervals (CIs) of the ratio of log transformed parameters are repor ted. ResultsINR and platelet aggregation were not affected by administration of ginkgo or ginger alone. The mean (95% CI) apparent clearances of S-warfarin after warfarin alone, with ginkgo or ginger were 189 (167-210) ml h -1 , 200 (173-227) ml h -1 and 201 (171-231) ml h -1 , respectively. The respective apparent clearances of R-warfarin were 127 (106-149) ml h -1 , 126 (111-141) ml h -1 and 131 (106-156) ml h -1 . The mean ratio (90% CI) of apparent clearance for S-warfarin was 1.05 (0.98-1.21) and for R-warfarin was 1.00 (0.93-1.08) when coadministered with ginkgo. The mean ratio (90% CI) of AUC 0 -168 of INR was 0.93 (0.81-1.05) when coadministered with ginkgo. The mean ratio (90% CI) of apparent clearance for S-warfarin was 1.05 (0.97-1.13) and for R-warfarin was 1.02 (0.95-1.10) when coadministered with ginger. The mean ratio (90% CI) of AUC 0 -168 of INR was 1.01 (0.93-1.15) when coadministered with ginger. The mean ratio (90% CI) for S-7-hydroxywarfarin urinary excretion rate was 1.07 (0.85-1.32) for ginkgo treatment, and 1.00 (0.81-1.23) for ginger coadministration suggesting these herbs did not affect CYP2C9 activity. Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin. ConclusionsGinkgo and ginger at recommended doses do not significantly affect clotting status, the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects.X. Jiang et al. 42659 :4 Br J Clin Pharmacol

Uninformed Complementary and Alternative Supplement Use: A Risky Behavior for Cardiovascular Patients

“…Garlic was shown to be safe if carefully monitored, ginseng was shown to significantly increase the clearance/bioavailability of S-warfarin (data that gives cause for further studies), and ginkgo biloba was shown to present no significant health risk in the study group. However, further studies in the elderly were suggested (Candelario-Jalil et al, 2006;Jiang et al, 2005Jiang et al, , 2006Macan et al, 2006;Wolf, 2006).Where some studies and reports found a safety risk and some did not, all found the need for further development and research in the area of CAS-drug interactions (CambriaKiely, 2002;Candelario-Jalil et al, 2006;Jayasekera et al, 2005;Jiang et al, 2005Jiang et al, , 2006Kruth et al, 2004;Lesho et al, 2004;Macan et al, 2006;McClaskey & Michalets, 2007;Rozenfeld et al, 2004;Wolf, 2006).…”

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

“…93,94 Ang-Lee et al identified increased potential for bleeding with ginkgo extracts and recommended discontinuation 36 hours before surgery. 95 The American Society of Anesthesiologists recommends patients discontinue herbal medicines (including ginkgo) 2 weeks before elective surgery.…”

Cancer Prevention Through Employ of Appropriate Diet in Daily Schedule

“…Taste and aroma of ginger may be calming. Large doses of ginger have been shown to have antiplatelet activity [13].…”

“…Large doses potentially harmful stomach pain, gas, vomiting, and inhibition of platelet formation [13].…”