Nonlinear dobutamine pharmacokinetics in a pediatric population

OBJECTIVETo evaluate a linear kinetic model for dobutamine clearance. DESIGNA prospective evaluation of pediatric patients receiving continuous infusions of dobutamine at varying doses. SETTINGA pediatric critical care unit. PATIENTSTwelve 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 μg/kg-min. MEASUREMENTS AND MAIN RESULTSSerum 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 do-pamine 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. CONCLUSIONSDobutamine 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. (Crit Care Med 1991; 19:871)