Hirt M N, Eschenhagen Thomas
Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg.
Dtsch Med Wochenschr. 2010 May;135(19):971-6. doi: 10.1055/s-0030-1253686. Epub 2010 May 5.
Vernakalant is a promising novel antiarrhythmic intravenous drug for the rapid conversion of atrial fibrillation to sinus rhythm. It blocks several ion currents important in cardiac action potential including IKr. Its difference to traditional antiarrhythmic drugs is a preferential effect on the atria, achieved by an inhibition of repolarizing potassium ion currents I(Kur), which is atrial-specific, and I(to), predominantly affecting atrial repolarization, as there is little atrial plateau potential. Furthermore vernakalant blocks frequency- and voltage-dependent sodium ion currents (I(Na)). Thus rapid action potentials in atrial fibrillation are particularly targeted by vernakalant: this leads to a conversion rate to sinus rhythm in about 50 % of recent-onset attacks (less than 7 days) of atrial fibrillation. Age, gender, organ function and concomitant medication seem to have no clinically significant influence on the pharmacokinetics of vernakalant. The number of patients included in the studies is still too small to provide a definitive answer on its cardiac toxicity. However, a demonstrated tendency towards proarrhythmia and little experience with this new drug demands precaution even after it has been officially approved.
维纳卡兰是一种很有前景的新型抗心律失常静脉用药，用于将房颤快速转复为窦性心律。它可阻断心脏动作电位中几种重要的离子电流，包括IKr。它与传统抗心律失常药物的不同之处在于，它对心房具有优先作用，这是通过抑制复极化钾离子电流IKur（这是心房特异性的）和I(to)（主要影响心房复极化，因为心房平台电位很小）来实现的。此外，维纳卡兰还可阻断频率和电压依赖性钠离子电流I(Na)。因此，房颤中的快速动作电位是维纳卡兰的特别作用靶点：这使得在约50%的近期发作（小于7天）的房颤中可转复为窦性心律。年龄、性别、器官功能和合并用药似乎对维纳卡兰的药代动力学没有临床显著影响。纳入研究的患者数量仍然太少，无法就其心脏毒性给出明确答案。然而，即使在该药正式获批后，已证实的致心律失常倾向以及对这种新药的经验不足仍需要谨慎使用。
