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Dofetilide-d4 is intended for use as an internal standard for the quantification of dofetilide by GC- or LC-MS. 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

1.Jurkiewicz, N.K., and Sanguinetti, M.C.Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agentCirculation Research72(1)75-83(1993) 2.Nalos, L., Varkevisser, R., Jonsson, M.K., et al.Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytesBritish Journal of Pharmacology165(2)467-478(2012) 3.Dunnink, A., van Opstal, J.M., Oosterhoff, P., et al.Ventricular remodelling is a prerequisite for the induction of dofetilide-induced torsade de pointes arrhythmias in the anaesthetized, complete atrio-ventricular-block dogEuropace14(3)431-436(2012)

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