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Dofetilide is a class III antiarrhythmic agent that prolongs cardiac action potential duration by selectively inhibiting the rapidly activating inward rectifying component of net delayed rectifier K+ current (IC50 = 31.5 nM in guinea pig cardiomyocytes).1 However, at 1 μM, dofetilide has pro-arrhythmic activity, inducing early afterdepolarizations (prolonged repolarization) in cell models and Torsade de Pointes in a rabbit screen for proarrhythmic properties when administered at a dose of 10 mg/kg.2 Formulations containing dofetilide have been used in the treatment of highly symptomatic atrial fibrillation and the conversion of flutter to normal sinus rhythm.3
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1. Rate-
2. Comparison of the IKr blockers moxifloxacin, dofetilide and E-
3. Ventricular remodelling is a prerequisite for the induction of dofetilide-