大豆异黄酮对华法林在人体内药动学和药效学的影响

目的:研究大豆异黄酮对华法林在人体内药动学和药效学的影响。方法:采用随机、单盲、双周期交叉、安慰剂对照试验设计。12名健康志愿者(男女各半)随机分为2组,连续5 wk每日分别服用大豆异黄酮胶囊(75 mg)或安慰剂1粒;d 29口服单剂量华法林5 mg;第2周期2组交叉服用安慰剂或大豆异黄酮胶囊,其余给药方案不变。按要求收集志愿者血样,分别以高效液相色谱(HPLC)法测定华法林的血药浓度以及半自动血凝仪测定常见凝血指标。结果:合用大豆异黄酮后,华法林的药动学参数c_(max)、AUC_(0～144)、AUC_(0～∞)、t_(1/2)显著增加(P<0.05),CL(F)显著域小(P<0.05),t_(max)和V_d(F)没有显著变化;华法林的药效学参数均无显著变化。单独服用大豆异黄酮4 wk后,凝血酶原时间(PT)和活化部分凝血活酶时间(APTF)无显著变化。结论:大豆异黄酮可影响华法林的药动学,但不影响华法林的药效学;单独服用大豆异黄酮4 wk对凝血功能无明显影响。

Effects of soy isoflavone on pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers

AIM:To study the effects of soy isoflavone on the pharmacokinetics and pharmacodynamics of warfarin and observe the anticoagulant activity of soy isoflavone.METHODS:A randomized,double-blinded, placebo-controlled,two-way cross-over trial was conducted.Twelve healthy volunteers (sex ratio was 1:1) were randomized into two groups and received soy isoflavone (75 mg,qd) or placebo (one pill,qd) for 5 wk respectively.The subjects received a single dose of warfarin (5 mg) on the day 29.Blood samples for pharmacokinetics and pharmacodynamics assessment were collected.RESULTS:Compared with placebo,soy isoflavone increased c_(max),AUC_(0-144),AUC_(0-∞),t_(1/2) of warfarin significantly(P<0.05 and decreased CL (F) of warfarin significantly (P<0.05),and there were no significant difference of V_d(F).Soy isoflavone had no significant pharmacodynamics effects on warfarin and had no effects on prothrombin time (PT) and activated partial thromboplastin time(APTT).CONCLUSION:Soy isoflavone has limited effects on the pharmacokinetics but no effects on the pharmacodyna mies of single dose warfarin in healthy subjects.Soy isoflavone has no effects on clotting process alone.