Cimetidine inhibition of ethmozine metabolism

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Abstract
Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine were investigated. Eight healthy men 22-40 yr old (.hivin.X = 27.6 yr) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days after cimetidine, 300 mg 4 times a day for 7 days. Plasma samples were drawn over the next 24 h for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8 and 24 h after each dose. After cimetidine, ethmozine clearance fell from 38.2 .+-. 10.7 to 19.7 .+-. 4.2 ml/kg per min and the t1/2 [half-time] increased from 3.3 .+-. 1.3 to 4.6 .+-. 1.6 h. 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. Cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.