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


METHODS
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.


RESULTS
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). However, SV increased significantly at the dobutamine plasma concentrations produced by the lowest infusion rate but remained mostly stable or even decreased thereafter. Although clinically slight, the overall increase in SV was statistically significant (r(2) = 0.062; p < 0.05).


CONCLUSIONS
Low plasma concentrations of dobutamine resulted in an increase in CO almost solely due to improved left ventricular contractility. However, at higher plasma concentrations of dobutamine, SV remained stable or even decreased, and the linear increase in CO was entirely based on increased HR.
Ahonen
Jouni
J
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland. jouni.ahonen@fimnet.fi
Aranko
Kari
K
Iivanainen
Aija
A
Maunuksela
Eeva-Liisa
EL
Paloheimo
Markku
M
Olkkola
Klaus T
KT
D000328:Adult; D019540:Area Under Curve; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004280:Dobutamine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D004280:Dobutamine