Pharmacokinetic-pharmacodynamic relationship of dobutamine and heart rate, stroke volume and cardiac output in healthy volunteers.

Clinical Drug Investigation
Jouni AhonenKlaus T Olkkola

Abstract

Dobutamine causes an increase in cardiac output (CO) by augmenting stroke volume (SV) through enhanced left ventricular contractility and by decreasing systemic vascular resistance. However, in some patients, the dominant mechanism by which dobutamine improves left ventricular performance is an increase in the subject's heart rate (HR). We therefore decided to evaluate the pharmacokinetic-pharmacodynamic relationship of dobutamine plasma concentrations and heart rate, SV and CO in healthy volunteers. We enrolled 23 subjects who received dobutamine at a dose of 2.5, 5 and 10 microg/kg/min for three consecutive periods of 60 minutes each. Dobutamine plasma concentrations were determined from 22 blood samples drawn during each study session. Echocardiography was used to measure CO before administration of dobutamine and once during each infusion period. There was a clear linear relationship between dobutamine plasma concentrations and CO (r(2) = 0.628; p < 0.001). In most subjects, HR remained stable at dobutamine plasma concentrations produced by the lowest infusion rate but increased markedly thereafter so that overall there was a linear relationship between dobutamine plasma concentrations and HR (r(2) = 0.540; p < 0.001). Howe...Continue Reading

References

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Citations

Jun 13, 2013·Pharmacology & Therapeutics·Hoshang Farhad, Venkatesh L Murthy
Mar 1, 2012·Toxicology and Applied Pharmacology·A R HarmerC E Pollard
May 17, 2018·Pharmacogenetics and Genomics·Dotan YogevMordechai Muszkat
Nov 21, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Anna C CrouchJoan M Greve
Nov 27, 2020·BMC Pharmacology & Toxicology·Günther KrumplJuri Hodisch
Feb 23, 2021·Journal of Diabetes and Its Complications·Johannes WikstromYixin Wang

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