Nalmefene to prevent epidural narcotic side effects in pediatric patients: A pharmacokinetic and safety study

Study Objective. To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects. Design. Double-blind, placebo-controlled study. Setting. University-affiliated children's hospital. Patients. Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia. Interventions. Patients were randomized to receive intravenous bolus nalmefene 1 μg/kg or placebo. Measurements and Main Results. Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2α)) was 0.36 ± 0.11 hour, the terminal elimination half-life (t(1/2β)) 8.7 ± 2.3 hours, clearance 0.729 ± 0.172 L/kg/hr, and steady-state volume of distribution 7.21 ± 2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-μg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention. Conclusion. Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.