Pharmacodynamics and onset of action of esmolol in anesthetized dogs

The pharmacodynamics and onset of action of esmolol, a novel, cardioselective beta adrenergic receptor antagonist with an ultra short duration of action, were studied in anesthetized dogs. Steady-state levels of beta blockade were attained within 10 min after initiation of esmolol infusion or when changing infusion rates. Similarly, steady-state blood levels of esmolol were attained within 30 min (the earliest sampling point) after starting an infusion and new steady-state blood levels were re-established again within 30 min after changing the infusion rates. Rapid recovery from beta blockade after termination of the esmolol infusion was paralleled by a rapid decline in blood levels of esmolol. The duration of action and elimination half-life both averaged less than 15 min. Excellent linear correlations were obtained between dose and steady-state blood concentration and the logarithm of the steady-state blood concentration and percentage of beta blockade. In a separate study, the onset of beta blockade with esmolol was observed within 15 sec of initiating a 60-sec infusion of 500 micrograms/kg/min. Peak beta blockade occurred at 30 to 45 sec after switching to a maintenance dose of 12.5, 25 or 50 micrograms/kg/min. The duration of peak effect was dependent on the maintenance dose. Peak blood levels of esmolol occurred immediately after stopping the loading dose and decreased to steady-state blood levels at 20 and 10 min after maintenance doses of 25 and 50 micrograms/kg/min, respectively. The results of these studies indicate that the onset, time to steady state and termination of beta blockade with esmolol are rapid and that an excellent correlation exists between the blood level of the drug and degree of beta blockade both during and after an esmolol infusion.