Antiarrhythmic plasma-concentration range of imipramine against ventricular premature depolarizations

The antiarrhythmic plasma-concentration range of imipramine with desmethylimipramine was determined in 15 cardiac patients with ventricular arrhythmias. When more than 80% efficacy was reached, subjects' plasma concentrations of imipramine and desmethylimipramine were determined by gas chromatography. The imipramine dose required for suppression of ventricular premature depolarizations (VPDs) ranged from 50 to 400 mg a day (1.6 to 3.9 mg/kg/day). Peak plasma imipramine concentration was reached at 2.5 +/- 0.92 hr and peak plasma desmethylimipramine concentration at 4.1 +/- 2.8 hr after imipramine. At 80%, VPD suppression, mean steady-state plasma concentration of imipramine with desmethylimipramine ranged from 74 to 385 ng/ml. The ratio of plasma imipramine to desmethylimipramine ranged from 0.5 to 5.5 (median = 1.3). The elimination t1/2 for the parent compound, imipramine, ranged from 4 to 14.4 hr. Imipramine is an effective antiarrhythmic drug with sustained duration of action, although its elimination t1/2 is relatively short.