Kathofer Sven, Thomas Dierk, Karle Christoph A
Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Cardiovasc Drug Rev. 2005 Fall;23(3):217-30. doi: 10.1111/j.1527-3466.2005.tb00167.x.
Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.
决奈达隆是一种非碘化苯并呋喃衍生物，其研发目的是克服常用抗心律失常药物胺碘酮与碘相关的局限性不良反应。它展现出广泛的细胞电生理作用谱，在很大程度上与胺碘酮相似，可抑制分离心肌细胞中的钾电流I(Kr)、I(Ks)、I(KI)、I(KACh)和I(sus)，以及钠电流和L型钙电流。此外，决奈达隆还具有抗肾上腺素能特性。在体内，决奈达隆在多种心律失常模型中已显示出比胺碘酮更有效，尤其是在预防缺血和再灌注诱发的心室颤动以及降低死亡率方面。然而，决奈达隆在犬类中导致尖端扭转型室速的发生率增加，这表明决奈达隆可能存在的促心律失常作用需要进一步评估。临床研究DAFNE、EURIDIS和ADONIS表明该药物在低风险患者中具有安全性、抗心律失常疗效和较低的促心律失常潜力。相比之下，已终止的ANDROMEDA试验中决奈达隆组死亡发生率增加，这引发了对充血性心力衰竭和中重度左心室功能不全患者安全性的担忧。决奈达隆似乎在预防心房颤动和心房扑动复发方面有效。尖端扭转型室速是与胺碘酮相关的最严重不良反应，在使用决奈达隆的人类患者中尚未有报道。与胺碘酮不同，决奈达隆在动物模型中对甲状腺功能和激素水平影响很小，在临床试验中对人体甲状腺功能也无显著影响。总之，决奈达隆可能是预防低风险患者心房颤动和心房扑动复发的有用药物。然而，需要进一步的实验研究和长期临床试验来提供决奈达隆疗效和安全性的更多证据。
