Cimetidine inhibition of ethmozine metabolism

Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.