目的 探討健康受試者參加華法林鈉片生物等效性試驗(yàn)的安全性。方法 收集2017—2020在首都醫(yī)科大學(xué)宣武醫(yī)院開展的4項(xiàng)隨機(jī)、開放、四周期、交叉對(duì)照設(shè)計(jì)的華法林鈉片生物等效性（BE）試驗(yàn)中188例受試者，比較空腹與餐后給藥所發(fā)生不良事件（TEAEs）的差異及TEAEs與性別和年齡的相關(guān)性。結(jié)果 4個(gè)試驗(yàn)中共報(bào)告了116例次TEAEs，與試驗(yàn)藥物相關(guān)的TEAEs 29例次，均屬于輕度，主要為凝血功能指標(biāo)異常（14例次）和肝功能指標(biāo)異常（10例次）。餐后給藥試驗(yàn)中肝功能指標(biāo)異常的發(fā)生例次多于空腹給藥試驗(yàn)（8：2），與試驗(yàn)藥物具有相關(guān)性的TEAEs發(fā)生率出現(xiàn)隨年齡增加而增高的趨勢(shì)。結(jié)論 健康受試者參加BE試驗(yàn)單次口服華法林鈉片的安全性良好，與試驗(yàn)藥物相關(guān)的不良事件多與華法林的藥理機(jī)制有關(guān)，年齡是不良事件發(fā)生類型和發(fā)生率的潛在影響因素。

Objective To investigate the safety of healthy subjects participating in the bioequivalence test of Warfarin Sodium Tablets. Methods A total of 188 subjects in a randomized, open, four-cycle, cross-control BE trial of Warfarin Sodium Tablets conducted in Xuanwu Hospital Capital Medical University from 2017 to 2020 were collected to compare the difference of adverse events (TEAEs) between fasting and postprandial administration and the correlation between TEAEs and sex and age. Results A total of 116 cases of TEAEs were reported in the four trials, and 29 cases of TEAEs related to experimental drugs were mild, mainly abnormal blood coagulation index (14 cases) and abnormal liver function index (10 cases). The incidence of abnormal liver function in postprandial administration test was higher than that in fasting administration test (8:2). The incidence of TEAEs related to experimental drugs increased with age. Conclusion A single oral administration of Warfarin Sodium Tablet in healthy subjects was safe. Most drug-related adverse events were caused by the pharmacological mechanism of warfarin, and subject's age was a potential factor influenced the type and incidence of adverse events.

R965.2

北京市醫(yī)院管理中心“登峰”計(jì)劃專項(xiàng)經(jīng)費(fèi)資助（DFL20190803）；首都科技領(lǐng)軍人才（Z191100006119017）；北京市醫(yī)院管理中心“青苗”計(jì)劃專項(xiàng)經(jīng)費(fèi)資助（QMS20200811）；首都衛(wèi)生發(fā)展科研專項(xiàng)（首發(fā)2022-2Z-20113）