Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

Abstract

1. The kinetics and dynamics of long acting propranolol 80 mg and 160 mg were examined after single oral doses to 12 healthy volunteers. 2. Long acting propranolol 160 mg produced a twofold increase in mean peak blood propranolol concentration and AUC compared with the lower dose. There was no difference in elimination half‐life, bioavailability and mean residence time of propranolol between the two doses. 3. Resting pulse rate was decreased by long acting propranolol 160 mg but not by the lower dose. 4. Both preparations blocked exercise induced tachycardia during the entire observation period of 29 h. Percentage inhibition of exercise tachycardia was significant at all time points but long acting propranolol 160 mg exhibited a greater reduction at 24 h and 29 h. 5. Increase in systolic blood pressure during exercise was inhibited by both preparations during the entire observation period with no differences between them. 6. The doubling of the dose administered was reflected in blood concentrations but not in pharmacodynamic parameters. Few pharmacodynamic differences were found between the two doses.

An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron‐Induced Cardiovascular Effects

“…This is a well‐recognized pharmacological response for β 1/2 ‐AR blockers in humans . The interpretation of the current study data for PD interaction of supratherapeutic exposures of mirabegron with doses of β 1/2 ‐AR blockers that have shown clear β 1 ‐AR blocking pharmacology in other studies suggests that the increases in HR most likely are related to stimulation of the cardiac β 1 ‐AR in a direct way.…”