St John's wort significantly increased the apparent clearance of S-warfarin (mean ratio 1.29; 90% CI 1.16-1.46) and reduced the pharmacological effect of warfarin, whereas ginseng had no effect.
RCT (n=12)
Open-label
three-way crossover
Does St John's wort or ginseng alter the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects?
St John's wort, but not ginseng, significantly increases the clearance of warfarin and reduces its pharmacological effect, highlighting a clinically relevant drug-herb interaction.
Effect estimate: Mean ratio 1.29 (95% CI 1.16-1.46)
Absolute Event Rate: 270% vs 198%
UNLABELLED: M: The aim of this study was to investigate the effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin. 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 14 days' pretreatment with St John's wort, or 7 days' pretreatment with ginseng. Dosing with St John's wort or ginseng 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 90% confidence intervals are reported. RESULTS: INR and platelet aggregation were not affected by treatment with St John's wort or ginseng. The apparent clearances of S-warfarin after warfarin alone or with St John's wort or ginseng were, respectively, 198 +/- 38 ml h(-1), 270 +/- 44 ml h(-1) and 220 +/- 29 ml h(-1). The respective apparent clearances of R-warfarin were 110 +/- 25 ml h(-1), 142 +/- 29 ml h(-1) and 119 +/- 20 ml h(-1) corrected. The mean ratio and 90% confidence interval (CI) of apparent clearance for S-warfarin was 1.29 (1.16, 1.46) and for R-warfarin it was 1.23 (1.11, 1.37) when St John's wort was coadministered. The mean ratio and 90% CI of AUC(0-168) of INR was 0.79 (0.70, 0.95) when St John's wort was coadministered. St John's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers. CONCLUSIONS: St John's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac-warfarin. Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin.
Jiang et al. (Tue,) conducted a rct in Healthy subjects (n=12). St John's wort or ginseng with warfarin vs. Warfarin alone was evaluated on Apparent clearance of S-warfarin (ml/h) (Mean ratio 1.29, 95% CI 1.16-1.46). St John's wort significantly increased the apparent clearance of S-warfarin (mean ratio 1.29; 90% CI 1.16-1.46) and reduced the pharmacological effect of warfarin, whereas ginseng had no effect.