基于不良反应监测大数据的中药药源性肝损伤风险信号新发现及易感因素初探  

Exploring new risk signals and susceptibility factors of traditional Chinese medicine-induced hepatotoxicity based on big data from adverse reaction monitoring

作　　者：郭龙鑫 高云娟 吴承钊 龙敏娟 祝胜凯 宋海波 赵旭 肖小河 GUO Longxin;GAO Yunjuan;WU Chengzhao;LONG Minjuan;ZHU Shengkai;SONG Haibo;ZHAO Xu;XIAO Xiaohe(China Military Institute of Chinese Materia,the Fifth Medical Centre,Chinese PLA General Hospital,Beijing 100039,China;College of Pharmacy,Dali University,Dali Yunnan 671000,China;Center for Drug Reevaluation,NMPA/NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance,Beijing 100076,China)

机构地区：[1]解放军总医院第五医学中心,全军中医药研究所,北京100039 [2]大理大学药学院,云南大理671000 [3]国家药品监督管理局药品评价中心,国家药品监督管理局药物警戒研究与评价重点实验室,北京100076

出　　处：《中国药物警戒》2024年第1期15-19,共5页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82230118);国家中医药管理局项目(ZYYCXTD-C-202005)。

摘　　要：目的探索基于国家不良反应监测大数据发现中药肝损伤风险信号的方式,初步筛选风险品种,并基于“三因致毒”理论分析其肝损伤的易感因素。方法对2012年1月1日至2016年12月31日收集的中药相关药物性肝损伤(DILI)的药品不良反应(ADR)报告进行回顾性分析,发现相关可疑中药品种,并预测可疑中药品种的肝损伤易感因素。结果共收集中药导致DILI的ADR报告1901份(1719例患者),新发现可疑中药品种237种,用于抗肿瘤的中药DILI发生率最高。给药途径以口服给药占比最大(71.70%),DILI的潜伏期的中位数为13.00 d,潜伏期以0~7 d(34.46%)最多。依据“三因致毒”理论分析发现可疑中药品种导致DILI与机体状态、药物本身和用药环境有关。结论发现系列中药风险信号,需要进一步对风险的确证和成因机制解析。Objective To explore the method of discovering signals of hepatotoxicity risk in traditional Chinese medicine(TCM)based on national adverse reaction monitoring big data,preliminarily screen risky varieties,and analyze the susceptible factors of liver damage based on the“Trielement Injury Hypothesis”theory.Methods Retrospective analysis of adverse drug reaction(ADR)reports related to TCM-induced drug-induced liver injury(DILI)collected between 2012 and 2016.Identify suspicious TCM varieties and predict the susceptible factors for liver damage in these varieties.Results A total of 1901 ADR reports(1719 patients)of TCM-induced DILI were collected,and 237 suspicious TCM varieties were newly discovered.Traditional Chinese medicine used for anti-tumor purposes had the highest incidence of DILI.The oral route of administration accounted for the largest proportion(71.70%),with a median latency period of 13.00 days,and the majority of cases had a latency period of 0 to 7 days(34.46%).Analysis based on the“Trielement Injury Hypothesis”theory revealed that the TCM varieties suspected of causing DILI were related to the body’s state,the drugs themselves,and the medication environment.Conclusion Discovery of a series of TCM risk signals requires further confirmation of the risk and analysis of the causal mechanisms.

关 键 词：中药 药品不良反应 三因致毒 肝损伤 抗肿瘤 风险信号 

分 类 号：R979.1[医药卫生—药品] R994.11[医药卫生—药学]