Is Metoprolol CR/ZOK More Selective Than Conventional Metoprolol and Atenolol?

Abstract

An alternative, simple method to assess beta 1-selectivity is to establish the impact of the beta blocker on beta 2-stimulated increases in plasma glucose and decreases in plasma potassium during an intravenous infusion of terbutaline. In the present study the effects of metoprolol CR/ZOK 100 mg, conventional metoprolol 100 mg, atenolol 100 mg, and placebo on these biochemical changes have been compared. In 12 healthy volunteers, terbutaline infusion of 6 micrograms/kg was administered intravenously over 1 hour. Three and a half hours before the infusion they were given a single dose of each of the four treatments in random order, single-blind. The maximum increase in plasma above baseline occurred at the end of a 60-minute terbutaline infusion. All three-beta blockers decreased the peak plasma glucose level achieved compared with placebo (P less than .01) but this reduction was significantly less with metoprolol CR/ZOK pretreatment than with atenolol (P less than .05). Similar results were seen for the AUC values for the curves obtained from the increments over the 60 minutes of the infusion and the subsequent 120 minutes after the infusion. In addition, both the AUC values and the maximum fall in potassium were significantly reduced by all treatments (P less than .05). The metoprolol CR/ZOK preparation produced significantly less effect than atenolol with respect to both AUC (P less than .05) and maximum fall (P less than .01) and significantly less effect than conventional metoprolol tablets in maximum fall (P less than .01). In conclusion, the metoprolol CR/ZOK formulation produces lower plasma concentrations and results in less effect on potassium and glucose compared to conventional metoprolol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of β-Blocker Titration on Glucose Homeostasis in Heart Failure

“…Terbutaline infusions offer an opportunity to explore hepatic glucose production in an experimental fashion. Similar to our findings, previous investigations have also reported a dose-related reduction in glucose concentrations with terbutaline stimulation and concomitant β-blocker administration 17, 19. Carvedilol is non-selective, and metoprolol is β 1 selective at lower doses.…”

“…Carvedilol is non-selective, and metoprolol is β 1 selective at lower doses. Previous studies reported that metoprolol is less β 1 selective at higher doses 17. According to their adrenergic receptor blocking pharmacology, one would anticipate more pronounced reduction of glucose AUC by carvedilol due to its non-selectivity and affinity to β 2 receptors 20.…”

A Risk-Benefit Assessment of Celiprolol in the Treatment of Cardiovascular Disease

“…However, at higher plasma concentrations even selective ~-blockers begin to block ~2-receptors. Thus, for example, the terbutaline-induced ~2-mediated fall in plasma potassium levels due to increased uptake into cells is blocked more by higher concentrations of a selective drug like metoprolol than by lower plasma concentrations (Kendall et al 1990;Smith et al 1983). Furthermore, at higher concentrations of selective agents the relative bronchosparing effects begin to be lost (Lofdahl et al 1988).…”

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

“…In a study of 1-selectivity, terbutaline infusions were given to 12 healthy subjects and 2-stimulated increase in plasma glucose and decrease in potassium were measured after pretreatment with metoprolol CR/ZOK (100 mg), conventional metoprolol (100 mg) and atenolol (100 mg) (29). All three -blockers decreased the peak plasma-glucose level compared with placebo, but the reduction was significantly less with metoprolol CR/ZOK compared to atenolol.…”