Is metoprolol CR/ZOK more selective than conventional metoprolol and atenolol?
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)
Kendall
M
M
Department of Pharmacology, Medical School, Edgbaston, Birmingham, United Kingdom.
Akhlaghi
S
S
Hughes
B
B
Lewis
H
H
D000328:Adult; D001262:Atenolol / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003692:Delayed-Action Preparations; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D016037:Single-Blind Method; D013607:Tablets; D013726:Terbutaline
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D011943:Receptors, Adrenergic, beta; D013607:Tablets; D001262:Atenolol; D008790:Metoprolol; D013726:Terbutaline; D011188:Potassium