Electropharmacology of amiodarone therapy initiation. Time courses of onset of electrophysiologic and antiarrhythmic effects

The time courses of onset of the electrophysiologic and antiarrhythmic effects of amiodarone were determined with serial electrophysiologic studies in 34 patients with inducible ventricular tachycardia. A standardized oral loading dosage was used for all patients (1,200 mg/day for 14 days; 800 mg/day for 7 days; and 400 mg/day thereafter). Eleven patients had the studies performed at baseline and after 2, 6, 10, and 20 weeks. Subsequently, 23 patients had studies at baseline and after 2 and 10 weeks. Changes in atrial, sinus, and atrioventricular nodal properties and in conduction intervals were maximal within 2 weeks (early effects). For example, atrioventricular nodal Wenckebach cycle length increased between baseline (369 +/- 80 msec) and 2 weeks (498 +/- 78 msec) (p less than 0.001) but did not change further after 10 weeks (500 +/- 89 msec). However, ventricular Class III effects required 10 weeks to become maximal (late effects). For example, the QT interval during atrial pacing increased between baseline (355 +/- 36 msec) and 2 weeks (406 +/- 37 msec) (p less than 0.001) and increased further after 10 weeks (436 +/- 45 msec) (p less than 0.001). Antiarrhythmic effects also followed different time courses of onset. Suppression of ventricular premature beats was maximal within 2 weeks. However, suppression of ventricular tachycardia inducibility and slowing of ventricular tachycardia rate was not maximal for 10 weeks. Correlations between serum desethylamiodarone concentrations and some late effects suggest that the mechanism of the time delay to maximal ventricular Class III effects may involve desethylamiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)