Rosen D A, Morris J L, Rosen K R, Nelson E R, Steelman R J, Gustafson R A, Wilhelm J A, Chang C T, Thackara J W, Frye R F
Pharmacotherapy. 2000 Jul;20(7):745-9. doi: 10.1592/phco.20.9.745.35207.
To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects.
Double-blind, placebo-controlled study.
University-affiliated children's hospital.
Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia.
Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo.
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(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 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-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention.
Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.
确定纳美芬在儿童中预防硬膜外麻醉引起的麻醉副作用的药代动力学及初步疗效。
双盲、安慰剂对照研究。
大学附属医院儿童医院。
34例接受心胸外科手术并采用硬膜外麻醉的儿童（年龄2 - 12岁）。
患者随机接受静脉推注纳美芬1微克/千克或安慰剂。
采集每位患者的6份血样（纳美芬给药前1份，以及从13个随机指定时间点采集的5份）以测定血浆纳美芬浓度。给药后24小时对患者的疼痛、恶心、呕吐及尿潴留情况进行评估。浓度 - 时间数据采用有限采样策略进行分析，以成人药代动力学参数作为贝叶斯先验值。使用ADAPT II软件对数据拟合二室一级模型。这些患者的药代动力学参数估计值与成人报道值相似。初始消除半衰期（t(1/2α)）为0.36±0.11小时，终末消除半衰期（t(1/2β)）为8.7±2.3小时，清除率为0.729±0.172升/千克/小时，稳态分布容积为7.21±2.49升/千克。1微克/千克剂量时未能证明预防硬膜外麻醉引起的副作用的能力。在疼痛、恶心、呕吐或尿潴留方面，研究组与安慰剂组之间未观察到统计学上的显著差异。
纳美芬在儿童中的药代动力学与成人相似。对这些患者给药安全，且未产生难以控制的疼痛。
