Pharmacokinetics of propranolol isomers and their relationships with beta adrenoceptor blocking activity in rabbits...

Plasma concentrations of dl- and l-propranolol were determined in rabbits after the i.v. injection of 200, 400 and 800 micrograms/kg of dl-propranolol. The data conformed to a biexponential equation. The beta adrenoceptor blocking activity was measured by the percent reduction in isoproterenolol-induced tachycardia after the administration of dl-propranolol. The l-isomer had a longer plasma half-life than dl-propranolol at each dose during the beta-phase. At a dose of 800 micrograms/kg, both dl- and l-propranolol had longer plasma half-life than those of 200 and 400 micrograms/kg doses and a smaller total plasma clearance was observed to 800 micrograms/kg, although statistically not significant. At steady state, plasma concentrations of both dl- and l-propranolol correlated well with beta adrenoceptor blocking activity (r = 0.913 for dl-propranolol and r = 0.939 for the l-isomer). These results demonstrate that after the administration of the racemic drug l-propranolol had a longer plasma half-life. The plasma concentration of dl- and l-propranolol is a good parameter for beta adrenoceptor blocking activity. The pharmacologic activity of propranolol at the highest dose persists longer than expected, probably due to hemodynamic alterations, which causes a decrease in liver blood flow with the resultant reduction in the elimination rate of the drug.