Relationship between plasma concentrations and suppression of ventricular extrasystoles by flecainide acetate (R-818), a new antiarrhythmic, in patients.

To assess the relationship between plasma levels of 2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benz-amide acetate (flecainide acetate), a new antiarrhythmic, and the suppression of ventricular arrhythmias, a decreasing multiple oral dosage regimen (200 mg b.i.d. to 50 mg b.i.d.) was administered over 12 days to eight patients with chronic ventricular extrasystoles. 1-h ECG recordings and blood samples for plasma flecainide measurements were obtained prior to, during each day of dosage, and post-drug. Maximum plasma levels observed with the higher doses range from 413 to 789 ng/ml (mean 637 ng/ml); these levels are well tolerated and are associated with essentially complete (greater than 95%) suppression of arrhythmias. As dose is decreased, plasma levels decline and the arrhythmias progressively return. The lowest plasma levels associated with essentially complete suppression of ventricular extrasystoles on two consecutive days range from 217 to 414 ng/ml (mean 317 ng/ml); levels below about 230 ng/ml are associated with the initial substantial reappearance (less than 70% suppression) of arrhythmias. These data suggest that the minimum therapeutic plasma levels of flecainide for ventricular extrasystoles range from about 200 to 400 ng/ml and that no consequential side effects are associated with plasma levels two-fold higher than these minimum levels.