Metoprolol in acute myocardial infarction. A pharmacokinetic and pharmacodynamic study

Summary A combined i.v. and oral dosage regimen of metoprolol early in acute myocardial infarction has been evaluated. Metoprolol 15 mg i.v. in three divided doses followed by 200 mg orally in divided doses was administered to 20 patients. The median delay from onset of pain to start of treatment was 7.5 h. Following the i.v. dose absorption of the first oral dose was prolonged in several patients, but the plasma metoprolol concentration rapidly stabilized at a mean of about 200 nmol/l. A significant correlation was found between the change in resting heart rate and the plasma concentration of metoprolol 15 min after the start of treatment. Blood pressure was not correlated with metoprolol concentration. Nine patients were restudied after 16–19 days of chronic therapy. The time to maximal plasma concentration of metoprolol on chronic treatment was reduced compared to that observed after the first oral dose. The median minimum plasma concentration during steady state averaged around 200 nmol/l and was comparable to the mean trough levels 24 and 48 h after the start of therapy. In the majority of patients, the dosage regimen rapidly produced and maintained plasma levels of metoprolol which should induce a significant degree of beta-blockade.