Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine

Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P less than 0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P less than 0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.