药物临床试验中健康受试者依非韦伦相关皮疹分析及文献回顾  

Analysis of efavirenz-related rashes in healthy subjects in drug clinical trials and literature review

作　　者：王琎 张兰[1] 胡朝英 Wang Jin;Zhang Lan;Hu Chaoying(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：《药物不良反应杂志》2023年第9期521-526,共6页Adverse Drug Reactions Journal

基　　金：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：目的探讨依非韦伦(EFV)在药物临床试验中致健康受试者皮疹的发生情况。方法对首都医科大学宣武医院药学部Ⅰ期临床研究中心2020年11月及2021年10月开展的2项以EFV为酶诱导剂的临床试验中,健康受试者EFV相关皮疹的发生情况进行回顾性分析。检索国内外相关数据库,收集以健康受试者为研究对象、以EFV为研究药物或酶诱导剂的研究文献,回顾文献中报道的EFV相关皮疹病例资料,并与本院2项临床试验中的数据汇总,进行描述性统计分析。结果2项临床试验共纳入40例健康受试者,5例(12.5%)发生EFV相关皮疹。从服药至出现皮疹的时间平均为8 d;皮疹首发症状均为皮肤瘙痒,出现部位主要为四肢和背部,主要形态为斑丘疹,无伴随其他症状及实验室检查异常。4例受试者退出试验,给予抗过敏及对症治疗5~7 d后皮疹消退;1例因皮疹较轻,给予炉甘石洗剂外用,继续参加试验,皮疹于17 d后(停用EFV 5 d)消退。检索到18篇以健康受试者为研究对象、以EFV为研究药物或酶诱导剂的文献。汇总后,18篇文献及本院研究共包括健康受试者403例,19例发生皮疹,皮疹发生率为4.7%。按EFV日剂量,600 mg/d组皮疹的发生率高于<600 mg/d组,但差异无统计学意义[5.5%(18/329)比1.4%(1/74),P=0.131];按服药时间,单次给药组和连续给药组皮疹的发生率相近[4.1%(4/97)比4.9%(15/306),P=0.753]。结论皮疹是健康受试者服用依非韦伦后常见的不良反应,严重程度一般较轻,及时发现和处理均可恢复。Objective To explore the occurrence of rashes in healthy subjects caused by efavirenz in drug clinical trials.Methods The occurrence of rashes related to efavirenz,which was used as an enzyme inducer,in healthy subjects in 2 clinical trials conducted by the Phase I Clinical Research Center of the Department of Pharmacy,Xuanwu Hospital,Capital Medical University(our hospital)in November 2020 and October 2021 was retrospectively analyzed.The relevant databases at home and abroad(up to November 30,2022)were searched,and the literature,in which efavirenz was applied as trial drug or enzyme inducer in healthy subjects,were collected.The cases of efavirenz-related rashes reported in the literature were reviewed.The clinical characteristics of the cases in the literature and above 2 clinical trials in our hospital were summarized and analyzed by descriptive statistics.Results A total of 40 healthy subjects were included in the 2 clinical trials,and 5(12.5%)developed efavirenz-related rashes.The average time from taking the medicine to the appearance of rashes was 8 days.The initial symptom was skin itching.The rashes occurred mainly on the limbs and back,and mainly presented as maculopapular rashes,without other symptoms or laboratory abnormalities.Four subjects withdrew from the trial and the rashes subsided after 5-7 days of anti-allergic and symptomatic treatments;one subject was given calamine lotion for external use because of mild rashes,and continued to participate in the trial.His rashes subsided 17 days later(5 days after stopping efavirenz).Eighteen literature in which efavirenz was used as a trial drug or enzyme inducer in healthy subjects were retrieved.A total of 403 healthy subjects collected from 18 literature and our trials were included in the analysis.Of them,19 subjects developed rashes,with a incidence of 4.7%.According to the daily dose of efavirenz,the incidence of rashes in the subjects of the 600 mg/d group was higher than that of the<600 mg/d group,but the difference was not statistically signif

关 键 词：健康志愿者 临床试验 药代动力学 药物相互作用 依非韦伦 药疹 安全性 细胞色素P-450酶诱导剂 

分 类 号：R969[医药卫生—药理学]