复方丹参滴丸对华法林在人体内药动学和药效学的影响

目的研究复方丹参滴丸对华法林在人体内药动学和药效学的影响,以及单独服用复方丹参滴丸4周后对凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)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名男性健康志愿者随机分为2组(6人/组),连续5周每日分别服用复方丹参滴丸(10片,每天3次)或安慰剂(10片,每天3次);d29口服单剂量华法林5 m g;第2周期2组交叉服用安慰剂或复方丹参滴丸,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法(H PLC)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。结果合用复方丹参滴丸后,华法林的药动学参数cmax、AUC0~144、AUC0~∞、t1/2显著增加(P<0.05),CL/F显著减小(P<0.05),tmax和V/F没有显著变化;华法林的药效学参数发生显著变化。单独服用复方丹参滴丸4周后,PT和APTT均发生显著变化。结论复方丹参滴丸可影响华法林的药动学和药效学;单独服用复方丹参滴丸4周对凝血功能有显著影响。

The Effects of Compound Danshen Dripping Pills on the Pharmacodynamics and Pharmacokinetics of Warfarin in Humans

Objective To study the effect of Danshen Dripping Pills on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not Danshen Dripping Pills alone has any anticoagulant activity. Methods A randomized, double-blind, placebo-controlled, two-way cross-over trial was designed.Twelve male healthy volunteers （6 person/group） were randomized to receive either Danshen Dripping Pills in the first treatment period and placebo in the second treatment period, or vice versa. In addition to their randomized trentment, all volunteers received a single dose of 5 mg warfarin on d 29 of each treatment period. Blood samples for assessment were taken at frequent intervals during each treatment period. Results Administration of Danshen Dripping Pills significantly increased cmax,AUC0-144、44,AUCc0-∞、t1/2 and significantly decreased CL/F of warfarin compared with placebo.In addition, Danshen Dripping Pills had chnically significant effect on the pharmacodynamic effects of warfarin, as assessed 144h after warfarin dosing by measurement of prothrombin time, activated partial thromboplastin time. Danshen Dripping Pills alone had significant effect on these indicators of the clotting process. Conclusion Usual doses of Danshen Dripping Pills seem to have significant effects on the pharmacokinetics and pharmacodynamics of single dose warfarin in healthy subjects.