Assessment of beta-blocking activity of trimepranol in man

The beta-blocking potency and the duration of action of trimepranol were measured in healthy volunteers using isoprenaline antagonism and reduction in exercise tachycardia. Based on isoprenaline antagonism, trimepranol was four times as potent as propranolol on a weight basis. The degree of beta blockade increased linearly with dose from 5 mg to 20 mg, excluding a dose-dependent first-pass metabolism in this dose range. There was a significnat correlation between plasma concentration and the effect of 14C-trimepranol on isoprenaline and exercise tests. The elimination half-life of trimepranol, calculated both on the basis of its effects and plasma concentrations, was approximately three to four hours. The beta blockade due to 10 or 20 mg of trimepranol was extended at least up to 12 hours following p.o. administration, based both on isoprenaline and exercise tests and on the effect of resting heart rate. Twice-a-day administration thus seems sufficient to provide a continuous beta blockade in the clinical use of trimepranol.