Nonlinear dobutamine pharmacokinetics in a pediatric population.
OBJECTIVE
To evaluate a linear kinetic model for dobutamine clearance.


METHODS
A prospective evaluation of pediatric patients receiving continuous infusions of dobutamine at varying doses.


METHODS
A pediatric critical care unit.


METHODS
Twelve patients age 2 days to 9 yrs and weighing 2.7 to 33 kg who required vasopressor therapy. Infusion rates for dobutamine ranged from 2 to 15 micrograms/kg.min.


RESULTS
Serum concentrations varied from 6.4 to 347 ng/mL (21 to 1151 nmol/L). Concentration was found to increase with dose. However, the relationship of clearance to steady-state concentration had a negative slope. Values for clearance varied from 32 to 625 mL/kg.min. Multiple analysis of variance on age, weight, and co-infused dopamine showed that these factors did not influence the relationship of clearance to steady-state concentration. Analysis to show an underlying model failed to differentiate Michaelis-Menten from nonlinear binding or mixed models on the basis of these data.


CONCLUSIONS
Dobutamine pharmacokinetics do not appear to follow a simple linear model. Based on the current data, neither age nor the added infusion of dopamine affects the clearance of dobutamine.
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University of Utah, Primary Children's Medical Center, Salt Lake City 84113.
Vernon
D D
DD
Minton
S D
SD
Dean
J M
JM
D000367:Age Factors; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004280:Dobutamine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D016014:Linear Models; D008657:Metabolic Clearance Rate; D008956:Models, Chemical; D011446:Prospective Studies; D011485:Protein Binding; D015203:Reproducibility of Results
D004280:Dobutamine; D004298:Dopamine