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决奈达隆:一种用于治疗心房颤动的新型抗心律失常药物。

Dronedarone: a new antiarrhythmic agent for the treatment of atrial fibrillation.

作者信息

Garcia Danielle, Cheng-Lai Angela

机构信息

Department of Pharmacy, Montefiore Medical Center, Bronx, NY, USA.

出版信息

Cardiol Rev. 2009 Sep-Oct;17(5):230-4. doi: 10.1097/CRD.0b013e3181b15ab9.

Abstract

In the armamentarium for rhythm control, amiodarone has been a mainstay of therapy for the management of atrial fibrillation (AF). Although amiodarone has shown to be effective in maintaining sinus rhythm, it has many extracardiac adverse effects. Dronedarone, a benzofuran amiodarone derivative, is structurally modified to reduce toxicities often associated with chronic amiodarone therapy. With the addition of a methylsulfonyl group, dronedarone is less lipophilic, has lower tissue accumulation, and a much shorter serum half-life of 24 hours compared with amiodarone. Dronedarone is also designed without the iodine moieties that are responsible for thyroid dysfunctions associated with amiodarone. Similar to amiodarone, dronedarone exhibits electrophysiologic characteristics of all 4 Vaughan Williams classifications. Phase III clinical trials have shown dronedarone to be effective at reducing ventricular rate, reducing recurrence of AF, and reducing cardiovascular morbidity and mortality in patients with AF or atrial flutter (AFL). However, dronedarone was associated with increased mortality in one study that included patients with severe heart failure (HL) and left ventricular dysfunction. Overall, dronedarone appears to be well tolerated. The most common side effects are gastrointestinal in nature and include nausea, vomiting, and diarrhea. Because of its more favorable adverse effect profile, dronedarone is likely to be a useful addition to the therapeutic management of AF. However, further comparative studies with amiodarone are needed to define dronedarone's place in therapy more clearly.

摘要

在节律控制的药物库中,胺碘酮一直是治疗心房颤动(AF)的主要药物。尽管胺碘酮已被证明在维持窦性心律方面有效,但它有许多心外不良反应。决奈达隆是一种苯并呋喃胺碘酮衍生物,其结构经过修饰以减少与慢性胺碘酮治疗相关的毒性。通过添加甲磺酰基,决奈达隆的亲脂性较低,组织蓄积较少,与胺碘酮相比,血清半衰期短得多,仅24小时。决奈达隆的设计还去除了与胺碘酮相关的甲状腺功能障碍的碘部分。与胺碘酮类似,决奈达隆具有所有4种 Vaughan Williams分类的电生理特性。III期临床试验表明,决奈达隆在降低心室率、减少房颤复发以及降低房颤或心房扑动(AFL)患者的心血管发病率和死亡率方面有效。然而,在一项纳入重度心力衰竭(HL)和左心室功能不全患者的研究中,决奈达隆与死亡率增加相关。总体而言,决奈达隆似乎耐受性良好。最常见的副作用是胃肠道方面的,包括恶心、呕吐和腹泻。由于其更有利的不良反应谱,决奈达隆可能是房颤治疗管理中的一种有用补充。然而,需要与胺碘酮进行进一步的比较研究,以更清楚地确定决奈达隆在治疗中的地位。

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