Reevaluation of digoxin‐encainide interactions using an animal model

Abstract

Summary: The effects of intravenous encainide on digoxin-induced atrial ectopic tachycardia (AET) were investigated in the rat using 3-channel simultaneous limblead electrocardiography. Pentobarbital-anesthetized (35 mg/kg, intraperitoneal) adult male rats were given digoxin subcutaneously, 30 mg/kg. After onset of AET, rats received either saline (0.5 ml/kg) or encainide; 0.25,0.5, 1 .O, or 2.0 mg/kg intravenously in repeated doses at 15-min intervals. At all doses, encainide converted digoxininduced AET to ventricular arrhythmias, prolonged recovery time, and increased mortality in comparison to salinetreated animals. An additional gmup of anesthetized rats was not given digoxin. These animals received encainide (2.0 mg/kg, intravenously) in repeated doses at 15-min intervals and developed dose-related increases in the P-R interval only. Blood samples were obtained by cardiac puncture from 12 additional anesthetized, digoxin-treated rats 5 min after the fourth intravenous dose of saline (0.5 ml/kg, n=6) orencainide (l.Omg/kg, n=6). Serum was prepared and analyzed by affinity column-mediated immunoassay. Digoxin levels were the same in both groups. These results suggest that encainide may exacerbate digoxin-induced arrhythmias (pmarrhythmic effect) in this species. In view of our findings of digoxin-encainide interactions in the rat, we recommend caution if these drugs are coadministered in humans.