Accumulation and adverse effects of metoprolol and propranolol after 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 AUC of the two last mentioned beta blockers behaved similarly (p less than 0.05). Measurement of exercise-induced tachycardia on the 6th day of administration showed no differences between monotherapy with the beta blocker and combined treatment with each of them and cimetidine. Except for one volunteer who complained of anxiety, weakness and sweating on the 6th day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers or in monotherapy with beta blockers.