Nonlinear dopamine pharmacokinetics in pediatric patients

Abstract

Dopamine steady-state concentrations were determined in 15 pediatric patients from 3 days to eight years of age receiving continuous infusions of dopamine. The first-order kinetic model does not accurately describe the kinetics of dopamine in these patients based on the finding that clearance varied as a function of concentration. A saturable protein binding model is described and provides a more accurate description of the behavior of the data. Using multivariate analysis, changes in dopamine kinetics were found as a function of weight. Furthermore, the co-administration of dobutamine altered the kinetics of dopamine. These data support the use of free dopamine concentrations rather than total concentration for studies of dopamine pharmacokinetics. Evaluation of total clearance of dopamine is of limited value, and changes in protein binding and intrinsic clearance must be considered in future studies of this drug.