AIM: The 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. METHODS: This 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 reported. RESULTS: INR 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. CONCLUSIONS: Ginkgo and ginger at recommended doses do not significantly affect clotting status, the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects

OBJECTIVE: To report a case of ginger-phenprocoumon interaction resulting in an elevated international normalized ratio (INR) and epistaxis. CASE SUMMARY: A 76-year-old white European woman on long-term phenprocoumon therapy with an INR within the therapeutic range began using ginger products. Several weeks later, she developed an elevated INR up to 10 and epistaxis. The INR returned to the normal range after ginger was stopped and vitamin K1 was given. DISCUSSION: There have been a number of investigations resulting in conflicting opinions on the effect of ginger on hemostasis, specifically, platelet inhibition. Nevertheless, based on these investigations, recommendations have been issued to refrain from ingesting ginger and other herbals like garlic or ginkgo biloba in situations where bleeding may be critical. An objective causality assessment revealed that the adverse drug event as a result of the phenprocoumon and ginger interaction was probable. CONCLUSIONS: As of writing, this was the first case report that may support an interaction between an oral anticoagulant and ginger together with a brief review of the literature on ginger and hemostasis. As this interaction was observed only by chance, this case highlights the importance of self-control of anticoagulation with coumarins particularly for the detection of unknown interactions