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  

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

作　　者：王琎 高琳艳 张兰[1] 胡朝英 WANG Jin;GAO Lin-yan;ZHANG Lan;HU Chao-ying(Phase I Clinical Trial Center,Department of Pharmacy,Xuanwu Hospital Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院药学部Ⅰ期临床研究中心,北京100053

出　　处：《现代药物与临床》2022年第9期1927-1931,共5页Drugs & Clinic

基　　金：北京市医院管理中心“登峰”计划专项经费资助(DFL20190803);首都科技领军人才(Z191100006119017);北京市医院管理中心“青苗”计划专项经费资助(QMS20200811);首都卫生发展科研专项(首发2022-2Z-20113)。

摘　　要：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。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 drugrelated 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.

关 键 词：华法林钠片 生物等效性试验 安全性 治疗引起的不良事件 凝血功能 肝功能 

分 类 号：R965.2[医药卫生—药理学]