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盐酸阿齐利特:一种新型III类抗心律失常药物。

Azimilide dihydrochloride: a new class III anti-arrhythmic agent.

作者信息

Abrol R, Page R L

机构信息

University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9047, USA.

出版信息

Expert Opin Investig Drugs. 2000 Nov;9(11):2705-15. doi: 10.1517/13543784.9.11.2705.

Abstract

Azimilide dihydrochloride (Stedicor) is a new class III anti-arrhythmic agent that is being developed by Proctor & Gamble to treat supraventricular and ventricular arrhythmias. Development of this agent is being undertaken due to the high prevalence of atrial fibrillation and the lack of satisfactory therapy for this arrhythmia, along with the desire to develop therapy to reduce the risk of life-threatening ventricular arrhythmias in patients following myocardial infarction. The mechanism of action of azimilide is to block both the slowly conducting (I(Ks)) and rapidly conducting (I(Kr)) rectifier potassium currents in cardiac cells. This differs from other class III agents that block I(Kr) exclusively or in combination with sodium, calcium, or transient outward (I(to)) potassium current channels. Azimilide is distinguished by a relative lack of reverse use-dependence, excellent oral absorption, no need for dose titration, an option for out-patient initiation, no need for adjustment associated with renal or liver failure and a lack of interaction with warfarin or digoxin. It carries some risk of torsade de pointes and rarely, neutropoenia. Azimilide has shown dose-related efficacy in prolonging the time to recurrence of atrial fibrillation. A large trial examining the impact of azimilide on mortality in high-risk patients following myocardial infarction has completed enrolment and should yield data in the next couple of years and further studies are planned. Even if this trial fails to show a survival benefit, a neutral effect on mortality will make the agent attractive for atrial arrhythmias.

摘要

盐酸阿齐利特(Stedicor)是一种新型III类抗心律失常药物,由宝洁公司研发,用于治疗室上性和室性心律失常。研发这种药物是因为心房颤动的高发病率以及针对这种心律失常缺乏令人满意的治疗方法,同时也希望开发出能降低心肌梗死后患者发生危及生命的室性心律失常风险的治疗方法。阿齐利特的作用机制是阻断心脏细胞中缓慢传导的(I(Ks))和快速传导的(I(Kr))整流钾电流。这与其他III类药物不同,其他药物仅阻断I(Kr)或与钠、钙或瞬时外向(I(to))钾电流通道联合阻断。阿齐利特的特点是相对缺乏反向使用依赖性、口服吸收良好、无需剂量滴定、可在门诊开始用药、无需因肾衰竭或肝衰竭进行调整,且与华法林或地高辛无相互作用。它有一些发生尖端扭转型室速的风险,很少发生中性粒细胞减少症。阿齐利特在延长心房颤动复发时间方面已显示出剂量相关的疗效。一项研究阿齐利特对心肌梗死后高危患者死亡率影响的大型试验已完成入组,预计在未来几年得出数据,并且还计划进行进一步研究。即使该试验未能显示出生存获益,对死亡率的中性影响也将使该药物对心房心律失常具有吸引力。

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