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

Study Objective. To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effe cts. Design. Double-blind, placebo-controlled study. Setting. University-affiliated children's hospital. Patients. Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic su rgery with epidural anesthesia. Interventions. Patients were randomized to receive intravenous bolus nalmef ene 1 mu g/kg or placebo. Measurements and Main Results. Six blood samples (one before nalmefene admi nistration and five from 13 randomly designated time points) from each pati ent were assayed to determine plasma nalmefene concentrations. Patients wer e assessed for pain, nausea, vomiting, and urinary retention for 24 hours a fter administration. Concentration-time data were analyzed by a limited sam pling strategy with adult pharmacokinetic parameters used as Bayesian prior s. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to v alues reported in adults. The initial disposition half-life (t(1/2 alpha)) was 0.36 +/- 0.11 hour, the terminal elimination half-life (t(1/2 beta)) 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-i nduced side effects could not be documented at the 1-pg/kg dose. No statist ically 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 unmanage able pain.