Effects of encainide and metabolizer phenotype on ventricular conduction during exercise

Genetic factors influence the extent of encainide metabolism. Approximately 93% of the Caucasian population extensively metabolize encainide to O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (MODE).¹ In extensive metabolizers, the steady-state plasma concentrations of ODE and MODE are higher than that of encainide during long-term therapy. In poor metabolizers, the metabolic profile is characterized by high concentrations of encainide, low concentrations of ODE, and absent MODE.². Encainide can produce marked prolongation of intraventricular conduction and this effect is rate-dependent.³ Previous data indicate that ODE and MODE are more potent than encainide in this regard.⁴ Consequently, the electropharmacologic effects of encainide would be expected to differ with respect to the genetically determined capacity to metabolize this drug. Thus, we postulated that extensive metabolizers of encainide would show more marked rate-dependent slowing of intraventricular conduction than would poor metabolizers. The present study determines if rate-dependent intraventricular conduction slowing could be demonstrated in patients receiving encainide during exercise-induced sinus tachycardia, and relates this effect to the genetic phenotype of encainide metabolism.