ABSTRACT
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.
Subject(s)
Hydrochlorothiazide/metabolism , Propranolol/metabolism , Adolescent , Adult , Animals , Biological Availability , Dogs , Drug Combinations/metabolism , Humans , Kinetics , Male , Species Specificity , TabletsABSTRACT
Nineteen healthy male volunteers were given daily 160 mg propranolol hydrochloride in divided doses, either four 40-mg tablets or two 80-mg tablets, and the plasma propranolol concentration profiles were compared after one and seven consecutive days of drug administration. The results indicate that the relative rate and extent of propranolol absorption were greater after 80 mg given twice daily than after 40 mg given four times per day. Both differences were statistically significant at steady state attained with the seven-day treatment. The variability in the areas under the concentration-time curves of propranolol appeared to be smaller after the 80-mg twice-a-day dosing schedule. The results are in accordance with the observed therapeutic equivalence of the two dosing regimens.
