中国药物警戒 ›› 2024, Vol. 21 ›› Issue (11): 1201-1208.
DOI: 10.19803/j.1672-8629.20240393

• 药源性心脏毒性研究专栏（二） • 上一篇    下一篇

非布司他心脏毒性的风险信号挖掘与实验观察

王雪1, 丁雪丽1, 鲁程锦1, 陈思颖1, 张晓朦1, 张冰1,2#, 林志健1,2,*   

  1. 1北京中医药大学中药学院,北京 102488;
    2北京中医药大学中药药物警戒与合理用药研究中心,北京 102488
  • 收稿日期:2024-06-17 出版日期:2024-11-15 发布日期:2024-11-20
  • 通讯作者: *林志健,男,博士,教授·硕导,中药药物警戒与合理用药。E-mail：linzhijian@bucm.edu.cn #为共同通信作者。
  • 作者简介:王雪,女,在读硕士,中药药物警戒与合理用药。
  • 基金资助:
    国家自然科学基金资助项目（82274117）; 国家中医药管理局中医药创新团队及人才支持计划子项（ZYYCXTD-C-202005-11）; 中央高校基本科研业务费专项资金（2024-JYB-JBZD-054）

Risk Signal Mining and Experimental Observations of Febuxostat Cardiotoxicity

WANG Xue1, DING Xueli1, LU Chengjin1, CHEN Siying1, ZHANG Xiaomeng1, ZHANG Bing1,2#, LIN Zhijian1,2,*   

  1. 1College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488 China;
    2Research Centre for Pharmacovigilance and Rational Use of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2024-06-17 Online:2024-11-15 Published:2024-11-20

PDF (PC)

276

摘要： 目的 挖掘美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)数据库的非布司他心脏不良事件,并结合实验观察,分析其风险特点,为降尿酸临床用药安全与警戒提供参考。方法 基于美国FAERS数据库2004年第1季度至2021年第3季度有关非布司他心脏不良事件报告,挖掘其风险信号。在高尿酸血症状态大鼠模型中,设置非布司他高剂量（7.2 mg·kg-1）、低剂量（3.6 mg·kg-1）2个组,观察生化检测中尿酸水平及相关心脏指标和组织病理,在降尿酸条件下观察其心脏风险。结果 美国FAERS数据库中共得到非布司他5 001份不良反应报告、15 989例不良反应,其中涉及与心脏相关的不良事件共992例,显示18个心脏风险信号。非布司他心脏毒性较多涉及男性,年龄大多发生在65岁以上。动物实验观察高尿酸状态下给予非布司他后大鼠尿酸水平显著降低,说明其具有良好的降尿酸疗效;心脏指标谷草转氨酶（AST）、肌酸激酶（CK）、心肌肌钙蛋白Ⅰ（cTn-I）水平升高,乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）水平降低,且Masson染色显示非布司他组出现不同程度的纤维化、蓝色胶原沉积明显。结论 临床使用非布司他治疗高尿酸血症的过程中需要关注其心脏风险,针对临床不同人群合理选用非布司他。

关键词: 非布司他, 心脏毒性, 尿酸, FAERS, 风险, 药物警戒

Abstract: Objective To evaluate the US spontaneous reporting system of cardiac adverse events of febuxostat, analyze the risks and provide data for safe use of uric acid-lowering drugs. Methods Based on the FAERS database reports of cardiac adverse events of febuxostat from Q1 2004 to Q3 2021, the risk signals were evaluated. In a rat model of hyperuricemia, high dose (7.2 mg·kg-1) and low dose (3.6 mg·kg-1) groups of febuxostat were set up to observe the uric acid level, related cardiac indexes and histopathology in biochemical tests. Results A total of 5 001 adverse reaction reports and 15 989 adverse reactions were retrieved from the FAERS database for febuxostat, and 992 of the adverse reactions with cardiac relevance had 18 cardiac risk signals. Febuxostat cardiotoxicity was more common in males and usually occurred among those over 65. In animal experiments, a significant reduction in uric acid levels was observed in rats administered with febuxostat in a hyperuricemic state, indicating a good uric acid-lowering effect. Such cardiac indicators as AST, CK and cTn-I increased, while LDH and CK-MB levels decreased. MASSON staining showed that the febuxostat groups appeared to have different degrees of fibrosis, with pronounced blue collagen deposition. Conclusion In the clinical use of febuxostat for the treatment of hyperuricemia, cardiac risks ought to be considered to ensure rational use of febuxostat in different clinical populations.

Key words: Febuxostat, Cardiotoxicity, Uric Acid, FAERS Datatase, Risk, Pharmacovigilance

中图分类号: