Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects

Abstract

AimThe aim of this study was to investigate the effect of St John's wor t and ginseng on the pharmacokinetics and pharmacodynamics of warfarin. 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 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. ResultsINR and platelet aggregation were not affected by treatment with St John's wor t or ginseng. The apparent clearances of S-warfarin after warfarin alone or with St John's wort or ginseng were, respectively, 198 ± 38 ml min -1 , 270 ± 44 ml min -1 and 220 ± 29 ml min -1 . The respective apparent clearances of R-warfarin were 110 ± 25 ml min -1 , 142 ± 29 ml min -1 and 119 ± 20 ml min -1 . 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. ConclusionsSt John's wort significantly induced the apparent clearance of both S-warfarin and Rwarfarin, 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. Warfarin interaction with St John's wort and ginsengBr J Clin Pharmacol 57 :5 593

Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men

“…The bioequivalence approach was used to determine clinically relevant interactions [15]. The pharmacokinetic parameters with and without metamizole treatment were compared by use of a two-tailed paired t-test after logarithmic transformation.…”

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

“…138 Reduced levels of digoxin also have been reported. 139 St. John's wort can alter anticoagulation properties of warfarin resulting in unstable INR values, 140 and bleeding complications were reported in elderly taking warfarin 141 (Table 2 and Online Supplemental Appendix 1). It can cause hypertensive crisis with foods rich in tyramine.…”

“…In 12 healthy subjects, ginseng treatment for 2 weeks did not affect either the pharmacokinetics or pharmacodynamics of a single 25-mg dose of warfarin. 140 Long-term effects of ginseng in elderly with comorbidities have not been systematically assessed. Because of the potential for platelet inhibition in humans, ginseng use should be discontinued in patients at least 1 week before surgery.…”

Interações entre fármacos e medicamentos fitoterápicos à base de ginkgo ou ginseng

“…Com base nestes relatos de casos, foram conduzidos três ensaios clínicos para avaliar a possível interação entre P. ginseng e varfarina em voluntários jovens. Dois ensaios clínicos mostraram que o ginseng não altera a farmacocinética e a farmacodinâmica da varfarina (Jiang et al, 2004;; porém, o outro estudo mostrou redução no efeito anticoagulante da varfarina, quando a mesma foi administrada juntamente com o ginseng (Yuan et al, 2004). Como os resultados destes estudos foram contraditórios, recomenda-se a monitoração do paciente, devido a possível redução da efi cácia dos anticoagulantes orais pelos medicamentos fi toterápicos à base de ginseng (Plotnikoff et al, 2004;Cheng, 2005;Micromedex, 2006).…”