The effect of cimetidine dose timing on oral propranolol kinetics in adults

Ten healthy male volunteers completed a study to determine the effect of cimetidine dose timing on the oral clearance of propranolol. Propranolol HCl 160 mg as tablets, was administered daily at 8 AM for 4 consecutive days on three occasions. In addition, cimetidine HCl 800 mg as tablets, was administered either simultaneously in the morning with propranolol (8 AM), at bedtime (10 PM), or not at all (control). Each treatment was separated by at least a 3-day washout. Propranolol and cimetidine serum samples were measured over the 24-hour dosing interval after the last propranolol dose. Cimetidine administration at 8 AM and 10 PM was associated with significant mean increases in the propranolol area under the serum concentration-time curve of 26% and 41%, respectively (P less than .002). The mean elimination half-life of propranolol was 6.3 hours during all three treatments. There was no significant difference in area under cimetidine serum concentration time curve between 8 AM and 10 PM dosing. Dosing cimetidine at bedtime 10 hours before propranolol does not diminish the magnitude of interaction.