ABSTRACT
Kinetic and dynamic data from 27 healthy male subjects were evaluated in a double-blind, randomized, double-crossover study to test the hypothesis that 180 mg/day propranolol twice and three times a day would provide much the same plasma levels and beta 1-blockade. The data indicate that propranolol twice rather than three times a day should be favored when beta 1-blockade is needed in therapy. The dynamic efficacy of the two schedules was the same and maximum concentration, AUC0-24, and 0-hr plasma propranolol values were higher after twice-than after three-times-daily dosing. The degree of beta 1-blockade (reduction in exercise tachycardia) was much the same on both dosing regimens at trough concentrations. These data indicate that both twice- and three-times-a-day dosing schedules provide well-sustained 24-hr beta-blockade and are probably interchangeable for therapeutic purposes.
Subject(s)
Propranolol/metabolism , Adult , Blood Pressure/drug effects , Double-Blind Method , Drug Administration Schedule , Heart Rate/drug effects , Humans , Kinetics , Male , Random AllocationABSTRACT
Experiments have been carried out in dogs and man to determine the effect of hydrochlorothiazide (HCT) on the pharmacokinetics of propranolol and to evaluate the bioavailability of two dosage forms containing both propranolol and HCT (40/25 and 80/25 mg, respectively). In adult male beagles, 50 mg of HCT had no apparent effect on AUC, Cmax, Tmax, and T1/2 of propranolol administered concurrently. In man, INDERIDE (40/25 mg) and INDERIDE (80/25 mg) were shown to be similar in bioavailability to the reference formulations, i.e. the same amount of drugs administered as the separate tablets of INDERAL plus HYDRODIURIL.
