THE PHARMACOKINETICS OF DOBUTAMINE IN PEDIATRIC INTENSIVE-CARE UNIT PATIENTS

Dobutamine is used for hemodynamic support in critically ill patients; however, due to the relative insensitivity of most available assays, there is little detailed information about its pharmacokinetics. We studied the pharmacokinetics of dobutamine in 27 children and infants using a high-sensitivity HPLC technique. The patients' ages ranged from 0.13 to 16.6 years; 17 received dobutamine for treatment of shock while 10 received it for treatment of post-cardiac surgery. Blood samples were collected before (N = 27) and after (N = 10, 9 time points each) the cessation of dobutamine infusion. The duration of dobutamine infusion before sampling was 1.87 +/- 0.29 days (range: 0.2-5.5; median: 1). The steady-state plasma concentration of dobutamine (infusion rate corrected to 5.0-mu-g/kg/min) was 105 +/- 19 ng/ml (range: 3.79-400; median: 76). The clearance rate was 151.1 +/- 47.5 ml/kg/min (range: 12.5-1319; median: 66). Most post-infusion time-concentration data were best fit to a biexponential function suggestive of a two-compartment model. The t1/2-alpha was 1.65 +/- 0.20 min (range: 0.64-3.01; median: 1.52) while the t1/2-beta was 25.8 +/- 11.5 min (range: 4.6-68.6; median: 16.9). Neither age, weight, sex, disease state, duration of infusion, nor blood measures of renal or hepatic dysfunction were found to be covariates of the above parameters. It was found, however, that the concomitant administration of dopamine altered dobutamine's pharmacokinetics, indicating the possible presence of a competitive component in dobutamine's disposition.