Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats

We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin lime was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8 +/- 0.5; ginseng 7.3 +/- 2.5 mu g mL(-1)), time to peak (control 2.6 +/- 1.0; ginseng 3.1 +/- 1.1 h), elimination half-life (control 14.3 +/- 5.8; ginseng 10.6 +/- 3.1 h), and oral clearance (control 17.5 +/- 3.3; ginseng 20.2 +/- 5.5 mL h(-1)) were not significantly different (P > 005). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776 +/- 619, ginseng 3830 +/- 362 s h) and maximum prothrombin time (control 57.2 +/- 11.8, ginseng 63.3 +/- 9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.