Effects of simultaneous administration of mexiletine and quinidine on the electrophysiologic parameters of canine Purkinje fibers.

The electropharmacologic effects of an equimolar combination of mexiletine and quinidine on canine Purkinje action potential parameters were compared with the effects of either drug alone in concentrations ranging from 0.31 to 5.0 X 10(-5) M. Six separate experiments were performed with mexiletine alone, quinidine alone, and the combination. At low concentrations, all three shortened action potential duration (APD) and effective refractory period (ERP) to the same degree; however, the combination depressed Vmax to the same extent as did solutions containing twice the concentration of quinidine alone even though mexiletine alone, in these concentrations, had no effect on the maximum rate of depolarization of phase 0 of the action potential Vmax. In higher concentrations, the combination depressed Vmax and prolonged the ERP to values midway between that achieved by the two drugs separately. Although increasing concentrations of mexiletine alone progressively shortened APD, the combination prolonged this parameter to values similar to those seen with twice the concentration of quinidine alone. The electropharmacologic effects of mexiletine and quinidine in combination are not simply additive and cannot be entirely predicted on the basis of a knowledge of their effects in isolation.