Dobutamine Alters the Pharmacokinetic and Pharmacodynamic Behavior of Esmolol

Abstract

Background and objective This study involved an investigation into the pharmacokinetic and pharmacodynamic behavior of esmolol in the presence of dobutamine in healthy subjects of European ancestry. Methods We conducted a single-center, prospective randomized study of 16 healthy subjects with each receiving an infusion of dobutamine sufficient to increase heart rate (HR) by 30 beats per minute (bpm) followed by a 60-minute infusion of 50 µg/kg/min esmolol. Pharmacokinetics, HR, and blood pressure were evaluated for 180 minutes. Results In the presence of dobutamine, esmolol elimination was substantially faster than without dobutamine, Esmolol infusion reduced dobutamine-induced elevation of HR reversibly whereas the dobutamine-induced systolic blood pressure (SBP) reduction did not recover after the termination of the esmolol infusion. No serious adverse events (AEs) were observed. Conclusions The accelerated elimination of esmolol was likely due to higher cleavage through tissue esterases induced by dobutamine-induced increased tissue passage cycles per time unit. The HR effect was characteristic of a beta-blocker, whereas the blood pressure effect was likely due to a mechanism other than direct beta-blockade. HR remained elevated after the infusion of esmolol and dobutamine, most likely due to persistent blood pressure reduction.

Keywords: cardioselective β-blocker; dobutamine; esmolol; pharmacodynamics; pharmacokinetics.

Figure 1. Time course of esmolol concentrations in whole blood in the presence and absence of dobutamine

Open squares and solid line: infusion of esmolol (50 µg/kg/min) on top of continuous dobutamine infusion; open circles and broken line: infusion of esmolol (50 µg/kg/min) only [8]. Please note that the elimination phase is lacking for the esmolol-only experiment, because infusion was continued at higher doses for an additional 23 hours

Figure 2. Time course of heart rate, and systolic and diastolic blood pressure

Open squares and solid line: heart rate; open diamonds and broken line: systolic blood pressure; open circles and dotted line: diastolic blood pressure BL: baseline