Abstract
Sematilide, a close structural analog of N-acetylprocainamide, prolongs cardiac action potentials in vitro, whereas it does not depress maximum action potential upstroke slope, a "class III" action. This report outlines an evaluation of the clinical pharmacologic actions of sematilide in 14 patients with chronic high-frequency nonsustained ventricular arrhythmias. In all, 36 intravenous infusions (range 0.15 to 1.5 mg/kg over 15 minutes) were administered in a dose-ranging, placebo-controlled study design. Sematilide prolonged rate-corrected QT (QTc) in a dose- and concentration-related fashion, did not alter PR or QRS, and slowed heart rate at high concentrations (≥2 μg/ml). The relations between dose and total area under the time-concentration curve, dose and peak plasma concentration, and peak plasma concentration and increase in QTc were linear (r = 0.66 to 0.92; p