华法林钠片在健康受试者生物等效性试验中的安全性分析

目的 探讨健康受试者参加华法林钠片生物等效性试验的安全性。方法 收集2017—2020在首都医科大学宣武医院开展的4项随机、开放、四周期、交叉对照设计的华法林钠片生物等效性（BE）试验中188例受试者，比较空腹与餐后给药所发生不良事件（TEAEs）的差异及TEAEs与性别和年龄的相关性。结果 4个试验中共报告了116例次TEAEs，与试验药物相关的TEAEs 29例次，均属于轻度，主要为凝血功能指标异常（14例次）和肝功能指标异常（10例次）。餐后给药试验中肝功能指标异常的发生例次多于空腹给药试验（8：2），与试验药物具有相关性的TEAEs发生率出现随年龄增加而增高的趋势。结论 健康受试者参加BE试验单次口服华法林钠片的安全性良好，与试验药物相关的不良事件多与华法林的药理机制有关，年龄是不良事件发生类型和发生率的潜在影响因素。

Safety analysis on bioequivalence studies of Warfarin Sodium Tablets in healthy subjects

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.