Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol

Abstract

Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol have been compared with those of atenolol. Metoprolol CR (100 mg and 200 mg), atenolol (50 mg and 100 mg) and placebo were each given once daily for four days in a double-blind, cross-over study to ten healthy men. The plasma concentration-time profiles were more even with metoprolol CR than with atenolol over the 24-h dose interval, shown by the lower fluctuation ratio and the longer time period during which the plasma concentration exceeded 50% of the maximum concentration. All four active treatment regimens reduced exercise heart rate over the 24-h period compared with placebo. However, the reduction in both exercise heart rate and systolic blood pressure (SBP) was more even with metoprolol CR than with atenolol. The remaining beta 1-blockade after 24 h, expressed as the percentage reduction in exercise heart rate in relation to placebo, was significantly greater after the administration of metoprolol CR, 200 mg, than after either dose of atenolol. At this time the beta 1-blockade with metoprolol CR, 100 mg, was similar to that with atenolol, 100 mg. At peak plasma concentrations, 4 h after the dose, the subjects experienced less fatigue during exercise with metoprolol CR than with atenolol.

Beta‐adrenoceptor blockade and hypoglycaemia. A randomised, double‐ blind, placebo controlled comparison of metoprolol CR, atenolol and propranolol LA in normal subjects.

“…Metoprolol CR is a new controlled-release formulation of metoprolol intended for once daily administration (Ragnarsson etal., 1987). It has a more even plasma concentration profile over 24 h compared with atenolol, and may confer improved ,13 selectivity in the first few hours after dosing (Blomquist et al, 1988).…”

Treatment with β‐blockers—the value of an even plasma concentration over 24 h

“…There are several studies (17,20,25) showing that metoprolol CR/ZOK has a more even plasma concentration compared with atenolol and conventional metoprolol tablets when administered once daily.…”

“…3), whereas the effect of 100 mg metoprolol CR/ZOK after 24 h did not differ from any of the atenolol dosages. In Figure 4 the trough to peak ratios of the mean percentage reduction in exercise induced tachycardia in relation to placebo are shown (17). The ratio was higher for the metoprolol CR/ZOK dosages compared with atenolol.…”

“…In this situation the only way to ensure proper blood pressure control at the end of 24 h is to give a large dose which would be likely to produce hypotension and other drug related adverse effects when the plasma concentration reaches its peak. When 1 selective -blockers are used in this way some loss of 1 selectivity can also be expected (15,17).…”

“…Metoprolol CR/ZOK has been formulated as an effective controlled-release preparation which achieves even 24-h plasma concentration (14,15,17,20). Atenolol and conventional metoprolol tablets also effectively reduce blood pressure, but the effect is most marked 2-4 h post-dosing and declines thereafter (17). Figure 1 shows the plasma concentrations of metoprolol and atenolol after adminstration of 100 mg metoprolol CR/ZOK, 100 mg conventional metoprolol tablets and 50 mg atenolol tablets in healthy subjects (20).…”