Duration of action of beta blockers

Three randomized, placebo-controlled, crossover experimental designs were used to define a suitable interdose interval and to study the adequacy of once-daily administration for applications in preventive trials on manifest or latent ischemic patients. Suppression of exercise tachycardia was used as the major effect variable. All measurements were made at different intervals after the last dose when the healthy subjects had been treated for at least 1 wk. Reductions of exercise tachycardia were found 24 hr after the last dose for atenolol, metoprolol, penbutolol, pindolol, propranolol, sotalol, and timolol. Penbutolol and propranolol induced equal reduction of exercise tachycardia at the end of the dose interval regardless of whether the total daily dose was given once daily or divided in 2 daily doses. Atenolol and sotalol, both with long half-lifes (t1/2s), were not superior to other beta blockers. Neither were slow-release preparations of metoprolol and propranolol markedly more effective 24 hr after the preparation than after ordinary tablets. Plasma concentration-time patterns after slow-release preparations may be important in patients with adverse experiences during peak plasma levels after conventional tablets.