Nonlinear dobutamine pharmacokinetics in a pediatric population.

Abstract

To evaluate a linear kinetic model for dobutamine clearance. A prospective evaluation of pediatric patients receiving continuous infusions of dobutamine at varying doses. A pediatric critical care unit. 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. 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. 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.