Effects on exercise tachycardia during forty‐eight hours of a series of doses of atenolol, sotalol, and metoprolol

Beta adrenoceptor blockers differ mainly in their plasma elimination half‐lifes (t½s). It has been assumed that drugs with longer t½s will have a longer duration of effect on exercise tachycardia. Several factors may influence the duration of action of beta blockers; we have investigated the contribution of plasma elimination t½ and dose by comparing the effects on an exercise tachycardia in healthy subjects of placebo, 25, 50, 100, and 200 mg of atenolol and of sotalol, and 50, 100, 200, and 400 mg metoprolol. Subjects exercized before and at 2, 3, 6, 8, 24, 33, and 48 hr after oral doses of each drug. Plasma samples for measurement of drug concentration were drawn before each exercise period. Twenty‐four hours after 50, 100, and 200 mg atenolol and 50, 100, 200, and 400 mg sotalol there were reductions in an exercise tachycardia; at this time reductions were greater after the larger doses. The plasma elimination t½s of atenolol were between 7.2 ± 1.2 and 9.1 ± 1.6 hr and for sotalol were 9.2 ± 0.7 and 10.1 ± 1.0 hr. Although 50, 100, and 200 mg metoprolol induced the same reductions in an exercise tachycardia 2 hr after drug as 25, 50, and 100 mg atenolol and 50, 100, and 200 mg sotalol, these doses were without effect at 24 hr. Metoprolol 400 mg reduced exercise tachycardia at 24 hr but the effect was less than that of the three largest doses of atenolol and sotalol. The plasma elimination t½ for metoprolol was between 3.6 ± 0.6 and 5.0 ± 1.8 hr. These results show that duration of cardiac beta blocking activity of atenolol, sotalol, and metoprolol is determined by the elimination t½ and dose. Clinical Pharmacology and Therapeutics (1981) 29, 295–302; doi: 10.1038/clpt.1981.39