Comparative pharmacodynamics and pharmacokinetics of conventional and long-acting propranolol.

This investigation was conducted to compare the pharmacokinetic and pharmacodynamic effects of single and multiple doses of conventional propranolol and long-acting propranolol in healthy human volunteers. Two double-blind, randomized, double-crossover, Latin square studies were carried out. One study evaluated long-acting propranolol 160 mg/d, conventional propranolol 40 mg qid, or placebo for seven days in 24 men. The other study compared long-acting propranolol 80 mg/d, conventional propranolol 20 mg qid, or placebo for seven days in 27 men. At specific times after the administration, blood samples were obtained, and heart rate and blood pressure were measured; exercise tests were done both on the first day and at steady state (day 7). In both studies, the area under the plasma propranolol concentration-time curve and the peak concentration were significantly less (P less than .0001) after the administration of long-acting propranolol compared with conventional propranolol on both day 1 and day 7; in addition, the elimination half-life was longer after administration of the long-acting preparation (9 hr) compared with that following the conventional dosage form (4 hr). Both conventional and long-acting propranolol significantly decreased the exercise heart rate at each of the selected time points (P less than .05) compared with placebo. Reduction in exercise heart rate was greater with conventional propranolol than with the long-acting formulation, but the differences were not statistically significant, when exercise was performed only at trough levels of the conventional drug. The decreases in exercise heart rate were correlated with plasma propranolol concentrations.

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use.

Long-acting propranolol (Inderal LA) is a new formulation of propranolol that allows release of the drug in a controlled manner, so that the plasma concentration at 24 hr after dosing is greater with long-acting propranolol than with conventional tablets. A single dose of 160 mg of long-acting propranolol can produce cardiac beta-adrenoceptor blockade throughout a 24 hr period without variability due to multiple peak concentrations. It has been shown that this formulation is as effective in the treatment of angina pectoris, hypertension and hyperthyroidism as the standard formulation. Studies with long-acting propranolol in cardiac dysrhythmias are lacking. This new dosage form would be a means of simplifying dosing regimens and thereby hopefully enhancing patient convenience and compliance.