Zhu M, Chan K W, Ng L S, Chang Q, Chang S, Li R C
Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT.
J Pharm Pharmacol. 1999 Feb;51(2):175-80. doi: 10.1211/0022357991772105.
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 time 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 microg 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>0.05). 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 sh) 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.
我们采用一种可靠的药代动力学/药效学方法，在大鼠模型中评估了一则关于人参和华法林之间药物相互作用的临床病例报告的意义。在雄性斯普拉格-道利大鼠中，研究了人参对单次给药（2 mg kg⁻¹）和稳态（每日0.2 mg kg⁻¹×6天）后口服华法林的药代动力学和药效学的影响。采用凝血酶原时间作为药效学指标。通过经过验证的高效液相色谱法测定华法林血浆浓度和人参提取物中的维生素K含量。在人参存在的情况下，单次给药后华法林的药代动力学未发生改变；血浆峰浓度（对照组7.8±0.5；人参组7.3±2.5 μg mL⁻¹）、达峰时间（对照组2.6±1.0；人参组3.1±1.1小时）、消除半衰期（对照组14.3±5.8；人参组10.6±3.1小时）和口服清除率（对照组17.5±3.3；人参组20.2±5.5 mL h⁻¹）无显著差异（P>0.05）。同样，在多次给药模式下未检测到华法林药代动力学的改变。在两种给药条件下，通过凝血酶原时间-时间曲线下面积（多次给药；对照组3776±619，人参组3830±362秒小时）和最大凝血酶原时间（对照组57.2±11.8，人参组63.3±9.1秒）评估，人参对华法林的药效学也无显著影响。此外，人参汤中未检测到维生素K含量。总之，目前在大鼠中获得的数据表明，人参与华法林同时给药时，对其药代动力学/药效学无显著影响。
