The pharmacokinetics of milrinone in pediatric patients after cardiac surgery

Background Milrinone has been shown to increase cardiac output in children after cardiac surgery, but pharmacokinetic analysis has not been used to id entify effective dose regimens. The purpose of this study was to characteri ze the pharmacokinetics of milrinone in infants and children and to apply t he results to the issue of dosing.,I Methods: Twenty children were studied after they underwent repair of congen ital cardiac defects. Control hemodynamic measurement was made after the ch ildren were separated from cardiopulmonary bypass, and each patient was giv en a loading dose of 50 mu g/kg progressively in 5 min. Hemodynamic measure ments were recorded again at the end of the loading dose and when a blood s ample was taken to determine milrinone plasma concentrations. Further blood samples were taken during the next 16 h for milrinone plasma concentration analysis. The pharmacokinetics of milrinone were analyzed using the popula tion pharmacokinetic program NONMEM. Results: The loading dose of milrinone resulted in a mean decrease hi mean blood pressure of 12% and a mean increase in cardiac index of 18% at a mean peak plasma concentration of 235 ng/ml. The pharmacokinetics of milrinone were best described by a three-compartment model. In the optimal model, all volumes and distribution clearances were proportional to weight, and weigh t-normalized elimination clearance was proportional to age; i.e., Cl1 = 2.5 . weight (1 + 0.058 . age) where Cl1 is expressed as ml/min, and the units of weight and age are kg and months, respectively. Conclusions: A loading dose of 50 mu g/kg effectively increases cardiac ind ex in children after cardiac surgery. Simulations indicate that the peak pl asma concentration can be maintained by following the loading dose of 50 mu g/kg with an infusion of approximately 3 mu g . kg(-1) . min(-1) for 30 mi n and then a maintenance infusion, which may require adjustment for age.