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本文引用的文献

1
In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation.用于抗生素诱导的QT间期延长风险评估的体外实验模型
Eur J Pharmacol. 2007 Dec 22;577(1-3):222-32. doi: 10.1016/j.ejphar.2007.07.070.
2
Preclinical electrophysiology assays of mitemcinal (GM-611), a novel prokinetic agent derived from erythromycin.新型促动力药物米替西奈（GM-611）的临床前电生理学检测，该药物源自红霉素。
J Toxicol Sci. 2007 Aug;32(3):217-30. doi: 10.2131/jts.32.217.
3
In vivo mechanisms precipitating torsades de pointes in a canine model of drug-induced long-QT1 syndrome.在药物诱导的长QT1综合征犬模型中引发尖端扭转型室速的体内机制。
Cardiovasc Res. 2007 Nov 1;76(2):247-56. doi: 10.1016/j.cardiores.2007.06.019. Epub 2007 Jun 29.
4
Combined pharmacological block of I(Kr) and I(Ks) increases short-term QT interval variability and provokes torsades de pointes.联合药理学阻断I(Kr)和I(Ks)会增加短期QT间期变异性并引发尖端扭转型室速。
Br J Pharmacol. 2007 Aug;151(7):941-51. doi: 10.1038/sj.bjp.0707297. Epub 2007 May 29.
5
Proarrhythmia as a class effect of quinolones: increased dispersion of repolarization and triangulation of action potential predict torsades de pointes.心律失常作为喹诺酮类药物的类效应：复极离散度增加和动作电位三角化可预测尖端扭转型室性心动过速。
J Cardiovasc Electrophysiol. 2007 Jun;18(6):647-54. doi: 10.1111/j.1540-8167.2007.00793.x. Epub 2007 Mar 28.
6
No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block.抗生素莫西沙星或阿奇霉素在患有慢性房室传导阻滞的麻醉犬中无促心律失常特性。
Br J Pharmacol. 2006 Dec;149(8):1039-48. doi: 10.1038/sj.bjp.0706900. Epub 2006 Nov 6.
7
Beat-to-Beat variability of repolarization determines proarrhythmic outcome in dogs susceptible to drug-induced torsades de pointes.复极的逐搏变异性决定了易发生药物诱导尖端扭转型室速犬的致心律失常结局。
J Am Coll Cardiol. 2006 Sep 19;48(6):1268-76. doi: 10.1016/j.jacc.2006.05.048. Epub 2006 Aug 28.
8
Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias.在药物诱导的心律失常的临床前评估中，对离体动脉灌注兔心室楔形组织进行盲法验证。
Heart Rhythm. 2006 Aug;3(8):948-56. doi: 10.1016/j.hrthm.2006.04.021. Epub 2006 Apr 22.
9
Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias.评估药物的致心律失常潜力：尖端扭转型室性心动过速心律失常模型和替代参数的现状
Pharmacol Ther. 2006 Oct;112(1):150-70. doi: 10.1016/j.pharmthera.2005.04.009. Epub 2006 May 22.
10
Use of arterially perfused rabbit ventricular wedge in predicting arrhythmogenic potentials of drugs.动脉灌注兔心室楔形组织在预测药物致心律失常潜力中的应用。
J Pharmacol Toxicol Methods. 2006 Nov-Dec;54(3):261-72. doi: 10.1016/j.vascn.2006.02.005. Epub 2006 Mar 6.

基于文献的四种用于评估药物致尖端扭转型室性心动过速风险的“硬终点”模型的评价

Literature-based evaluation of four 'hard endpoint' models for assessing drug-induced torsades de pointes liability.

作者信息

Vos M A

机构信息

Division Heart and Lungs, University Medical Center Utrecht, Alexander Numangebouw, Utrecht, The Netherlands.

出版信息

Br J Pharmacol. 2008 Aug;154(7):1523-7. doi: 10.1038/bjp.2008.277. Epub 2008 Jul 7.

DOI:10.1038/bjp.2008.277
PMID:18604235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2492098/
Abstract

In safety pharmacology, a number of preclinical models for detecting drug-induced proarrhythmia liability have been recently introduced that utilize hard endpoints: early after depolarziations (EADs), torsades de pointes (TdP) or both as the principal biomarker. To explore the validity of four of the most common of these models, (the isolated canine/rabbit left ventricular wedge preparation, the isolated rabbit heart, the methoxamine-pretreated anaesthetized rabbit and the complete, chronic AV-blocked (CAVB) dog (conscious and anaesthetized), the present article reviews published data sets for three drugs with recognized and different human TdP liabilities (cisparide, terfenadine and moxifloxacinin). Finally, this review considers the value of inclusion of analysis of beat-to-beat variability of repolarization (BVR) in TdP liability testing to improve sensitivity and specificity.

摘要

在安全药理学中，最近引入了一些用于检测药物致心律失常风险的临床前模型，这些模型利用硬性终点：早期后除极（EADs）、尖端扭转型室速（TdP）或两者作为主要生物标志物。为了探究这些模型中最常用的四种模型（离体犬/兔左心室楔形标本、离体兔心脏、甲氧明预处理的麻醉兔以及完全慢性房室传导阻滞（CAVB）犬（清醒和麻醉状态））的有效性，本文回顾了三种具有公认且不同人类TdP风险的药物（西沙必利、特非那定和莫西沙星）的已发表数据集。最后，本综述考虑了在TdP风险测试中纳入复极逐搏变异性（BVR）分析以提高敏感性和特异性的价值。