从国际药物监督数据库到iPSC心肌细胞的翻译研究
Joe-Elie Salem1,2,3, Tao Yang2,3, Javid J Moslehi2
1Assitance Publique Hopitaux de Paris, Pitié-Salpêtriére Hospital, Departments of Pharmacology and Cardiology, UNICO-GRECO Cardio-oncology Program, Centre d'investigation clinique-1421, Pharmacovigilance Unit (J-E.S., X.W., E.G., F.H-L., B.L-V., C.F-B.), INSERM, Sorbonne Université, Paris, France.
Circulation
|August 6, 2019
概括
雄激素缺乏治疗 (ADT) 增加了男性获得的长QT综合征 (aLQTS) 和torsades de pointes (TdP) 的风险. 在干细胞模型中,恩扎胺是一种ADT,与心脏事件和延长的QT间隔显著相关.
科学领域:
- 心脏病学
- 药理学
- 电生理学
背景情况:
- 男性的阴性腺体缺陷和雄激素缺乏疗法 (ADT) 与获得的长QT综合征 (aLQTS) 和torsades de pointes (TdP) 有关.
- 与ADT相关的ALQTS的临床特征和机制需要进一步阐明.
研究的目的:
- 研究ADT与LQTS和TdP等心律失常之间的关联.
- 探索ADT引起的心脏事件的潜在电生理机制.
主要方法:
- 在VigiBase药监数据库中搜索与ADT相关的不良事件.
- 利用诱导多能干细胞衍生的心肌细胞来研究ADT和二的电生理效应.
主要成果:
- 在VigiBase中确定了184例aLQTS和/或TdP,以及与ADT相关的99例突然死亡.
- 检查的十种ADT中,有七种与心脏事件有不成比例的关联;恩扎鲁胺与较高的死亡率有关.
- 恩扎胺显著延长了作用潜力的持续时间,诱导了脱极化,抑制了心肌细胞中的电流,增加了心肌细胞中的电流,而二测试则逆转了这些效应.
结论:
- 在接受恩扎胺和其他ADT治疗的男性中,QT延长和TdP具有显著的风险.
- 这些发现强调了接受ADT的患者需要仔细的心脏监测.
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