目的 基于美國(guó)食品藥品監(jiān)督管理局（FDA）公共數(shù)據(jù)開放項(xiàng)目（openFDA）中丁苯那嗪和氘丁苯那嗪不良事件的數(shù)據(jù)，分析2個(gè)藥物的安全性，為臨床用藥提供參考。方法 收集2017年1月1日—2022年12月31日FDA不良事件報(bào)告系統(tǒng)（FAERS）中丁苯那嗪與氘丁苯那嗪相關(guān)的不良事件報(bào)告，提取報(bào)告數(shù)排名前50位不良事件報(bào)告，采用報(bào)告比值比法（ROR）挖掘不良反應(yīng)風(fēng)險(xiǎn)信號(hào)。結(jié)果 共得到丁苯那嗪相關(guān)的不良事件報(bào)告1 468例，氘丁苯那嗪相關(guān)的不良事件報(bào)告3 097例，對(duì)報(bào)告數(shù)排名前50位不良事件進(jìn)行藥物不良反應(yīng)風(fēng)險(xiǎn)信號(hào)分析，分別檢測(cè)出丁苯那嗪39個(gè)不良反應(yīng)風(fēng)險(xiǎn)信號(hào)，氘丁苯那嗪35個(gè)不良反應(yīng)信號(hào)。按照不良事件報(bào)告數(shù)進(jìn)行排名，丁苯那嗪前5位的不良事件依次為超說(shuō)明書使用、死亡、藥物無(wú)效、抑郁、治療不服從；氘丁苯那嗪前5位的不良事件依次為藥物無(wú)效、運(yùn)動(dòng)障礙、抑郁、嗜睡、失眠。結(jié)論 氘丁苯那嗪通過(guò)結(jié)構(gòu)改造，優(yōu)化了藥動(dòng)學(xué)參數(shù)，減少了給藥劑量和頻次，從而明顯提高了患者的用藥依從性，檢測(cè)到的不良反應(yīng)風(fēng)險(xiǎn)信號(hào)與原型藥物相比有所減少，但需注意其自殺風(fēng)險(xiǎn)，提示臨床予以進(jìn)一步的安全性評(píng)價(jià)。

Objective To analyze the safety of tetrabenazine and deutetrabenazine based on openFDA to provide a reference for clinical use. Methods To collect the adverse event reports related to tetrabenazine and deutetrabenazine in the FDA Adverse Events Reporting System (FAERS) from January 1, 2017 to December 31, 2022, extract the top 50 adverse event reports, and the report odds ratio (ROR) was utilized for signal detection. Results A total of 1 468 cases of tetrabenazine-related adverse events and 3 097 cases of deutetrabenazine-related adverse events were reported to FAERS, and the top 50 adverse events were analyzed for adverse drug reaction risk signals, 39 adverse event risk signals were detected for tetrabenazine and 35 adverse event signals for deutetrabenazine, respectively. Top 5 adverse event reports for tetrabenazine were off label use, death, drug ineffective, depression, and treatment noncompliance. Top 5 adverse event reports for deutetrabenazine were drug ineffective, dyskinesia, depression, somnolence, and insomnia. Conclusion Deutetrabenazine significantly improved medication compliance by modifying and optimizing pharmacokinetic parameters to reduce the dose and frequency of administration, and the adverse reaction risk signals detected was reduced compared with tetrabenazine, but attention needs to be paid to its suicide risk, prompting further clinical safety evaluation.

R971

中國(guó)毒理學(xué)會(huì)臨床毒理專項(xiàng)（CST2020CT301）；北京市研究型病房建設(shè)示范單位項(xiàng)目（BCRW202010）