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Circulation, Vol 56, 980-984, Copyright © 1977 by American Heart Association

ARTICLES

Suppression of ventricular ectopic depolarizations by tocainide

RL Woosley, DG McDevitt, AS Nies, RF Smith, GR Wilkinson and JA Oates

In a previous clinical study we demonstrated that tocainide is effective in the suppression of ventricular ectopic depolarizations (VEDs) after single oral doses. This information provided the basis for evaluating this drug's antiarrhythmic efficacy after multiple dose administration according to a loading-maintenance regimen. Twelve patients with stable VEDs were given loading doses of tocainide (400- 600 mg) with maintenance doses every 12 hours. Every 48 hours the dose was increased until either arrhythmia suppression to less than 25% of VED frequency during placebo administration or side effects occurred. Computer analysis of 12-hr telemetric ECGs taken 24-36 hr after each dosage increment documented effective suppression (76-95%) in 8 of 12 patients. Those subjects demonstrating suppression were randomly assigned to a cross-over study of placebo or active drug at the dosage found effective in the dose-ranging phase. Dosages for the cross-over stage ranged from 400 to 1100 mg every 12 hours. Comparison of the two five-day periods documented suppression in these patients (mean +/- SE = 83.3 +/- 4%). No serious side effects or undue drug accumulation occurred during the study. The data indicate that tocainide can effectively suppress VEDs for 8-12 hours in many patients and that continuous suppression could be possible on an 8-12 hr dosage regimen.

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