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决奈达隆的临床药理学与电生理特性

[Clinical pharmacology and electrophysiological properties of dronedarone].

作者信息

Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S

机构信息

Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn.

出版信息

Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10.

Abstract

Dronedarone is a benzofuran derivative structurally similar to amiodarone but non-iodinated. The agent was systematically developed with the aim to maintain the antiarrhythmic potency of amiodarone while reducing the extracardiac side effects of the drug. Dronedarone is less lipophilic compared to the mother compound, which manifests in a substantial lower time to steady state (4-8 days compared to 1-3 weeks with amiodarone), and a more rapid elimination (half life 25-30 hours). Dronedarone has antiarrhythmic properties of all Vaughan-Williams classes. Among other channel blocking effects, It blocks sodium ion channels at higher stimulation frequency, prolongs the cardiac action potential, and has properties of a calcium channel blocker. Further, dronedarone has non-competitive antiadrenegic effects. No reverse use dependence has been documented at higher heart rate. These effects explain the antiarrhythmic and rate control properties of dronedarone in patients with atrial fibrillation.

摘要

决奈达隆是一种苯并呋喃衍生物,在结构上与胺碘酮相似,但不含碘。该药物是经过系统研发的,目的是在维持胺碘酮抗心律失常效力的同时,减少该药物的心脏外副作用。与母体化合物相比,决奈达隆的亲脂性较低,这表现为达到稳态的时间大幅缩短(与胺碘酮的1 - 3周相比为4 - 8天),以及消除更快(半衰期为25 - 30小时)。决奈达隆具有所有 Vaughan - Williams 分类的抗心律失常特性。在其他通道阻断作用中,它在较高刺激频率下阻断钠离子通道,延长心脏动作电位,并具有钙通道阻滞剂的特性。此外,决奈达隆具有非竞争性抗肾上腺素能作用。在较高心率时未记录到反向使用依赖性。这些作用解释了决奈达隆在房颤患者中的抗心律失常和心率控制特性。

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