Lorcainide; II. Plasma concentration‐effect relationship

Abstract

The effects of lorcainide were studied in 17 patients after single doses (2 mg/kg intravenously; 6 mg/min intravenously over 30 to 40 min; 150, 300, and 500 mg orally) and during long‐term antiarrhythmic treatment (200 to 600 mg daily orally). The frequency of ventricular premature contractions (VPCs), the changes in the electrocardiogram (ECG), and the plasma concentration of lorcainide were determined. The widening of the QRS complex observed after single doses of lorcainide mimicked the time course of plasma concentration permitting the construction of linear relationships between both parameters. After oral administration lower plasma concentrations were required to produce the same QRS widening than after intravenous administration. Patients differed considerably in the slopes of these plasma concentration‐effect curves. After repeated intravenous infusions of lorcainide, plasma concentration‐effect relationships were constructed for both antiarrhythmic and ECG effects. During drug infusion higher concentrations of lorcainide were required to induce antiarrhythmic and toxic effects (QRS widening and PQ prolongation) than during the postinfusion period. Whereas during the infusion period the plasma concentration‐effect curves for both effects followed the same slope, during the postinfusion period VPCs were remarkably more sensitive to plasma concentration than the changes in the ECG. Suppression of VPCs during long‐term treatment with lorcainide was accompanied by small changes in the ECG which were related to the dose and plasma concentration of lorcainide. Thus, the lorcainide regimen may be monitored by careful inspection of the ECG.