Electrophysiological effects of encainide and its metabolites in 11 patients

Encainide is a new antiarrhythmic class IC agent. Eleven patients were given 1 mg/kg of encainide i.v. over a 15-min period. Electrophysiological studies were done before and l h after drug administration. Blood levels of encainide and its principle metabolites O-demethyl-encainide, 3 metoxy-O-demetyl-encainide and N-demethyl-encainide were measured serially after drug administration. Heart rate, blood pressure, and conduction intervals were monitored. Sixty minutes after drug administration there was a marked increase of the QRS, PA, AH, and HV intervals of 28.1% (p less than 0.01), 17.2% (p less than 0.01), 22.4% (p less than 0.01), and 32.2% (p less than 0.01), respectively, and a slight increase of the Wenckebach cycle length of 8% (p less than 0.05). BP, RR, QT, CSNRT, ESACT, ERP, and FRP did not vary significantly. The HV interval already was increased significantly 2 min after drug administration, while AH was not increased until 15 min after drug administration. The average blood levels of encainide and ODE 60 min after drug administration were 0.410 +/- 0.12 and 0.176 +/- 0.09 microgram/ml, respectively (mean +/- SE of the mean). There was a positive correlation between the increase of the AH and the blood level of ODE, which points out the importance of prolonged electrophysiological studies when testing drug with possibly active metabolites.