ORIGINAL ARTICLE The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion Christopher J. Stemland 1 , Jurgen Witte 2 , Douglas A. Colquhoun 1 , Marcel E. Durieux 1 , Loralie J. Langman 3 , Ravi Balireddy 1 , Swapna Thammishetti 1 , Mark F. Abel 4 & Brian J. Anderson 5 1 Department of Anesthesiology, University of Virginia Charlottesville, VA, USA 2 Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Munster, Munster, Germany 3 Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA 4 Department of Orthopedic Surgery, University of Virginia Charlottesville, VA, USA 5 Department of Anaesthesiology, University of Auckland, Auckland, New Zealand Keywords children; methadone; pharmacodynamics; pharmacokinetics; scoliosis Correspondence Christopher Stemland, Department of Anesthesiology, University of Virginia, Charlottesville, VA 800710, USA Email: cjs9f@virginia.edu Section Editor: Per-Arne Lonnqvist Accepted 6 August 2012 doi:10.1111/pan.12021 Summary Background: The optimal methadone dosing regimen for children undergo- ing spinal surgery is uncertain because of sparse pediatric pharmacokinetic data and a paucity of analgesic effect data. The minimum effective analgesic concentration of methadone in opioid naı¨ve adults is 58 mcgL 1 . Methods: Adolescents aged 12–19 years undergoing idiopathic scoliosis cor- rection were administered 0.25 mgkg 1 racemic methadone IV prior to surgi- cal incision. Arterial blood samples for methadone assay were obtained at 0 min, 5 min, 10 min, 15 min, 20 min, 40 min, 1 h, 2 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, and 48 h. Compartment analysis was undertaken using nonlinear mixed effects models. Parameter estimates were standardized to a 70-kg person using allometric models. Results: A three-compartment linear disposition model best described observed time–concentration profiles. Population parameter estimates (between-subjects variability) were central volume (V1) 19.1 (126%) L 70 kg 1 , peripheral volumes of distribution V2 65.5 (60%) L 70 kg 1 , V3 485 (23%) L 70 kg 1 , clearance (CL) 9.3 (11%) Lh 1 70 kg 1 , and inter- compartment clearances Q2 282 (95%) Lh 1 70 kg 1 , Q3 139 (42%) Lh 1 70 kg 1 . The terminal elimination half-life was 44.4 h. The mean observed methadone concentration was <58 mcgL 1 by the first hour after administration. Conclusions: Current pharmacokinetic parameter estimates in adolescents are similar to those reported in adults. Methadone undergoes rapid redistri- bution after bolus administration. This may result in plasma concentrations that provide inadequate analgesia postoperatively. We would suggest follow- ing the bolus (0.25 mg.kg -1 ) with an infusion (0.1–0.15 mgkg 1 h 1 for 4 h) during spinal surgery to ensure adequate plasma concentrations for 24 h. Introduction Methadone is a long-acting opioid agonist that can provide sustained postoperative analgesia following complex spine procedures in adults (1) and major abdominal surgery in children (2). Methadone is cleared predominantly by the hepatic P450 cytochrome enzymes CYP2B6 and CYP3A4, and to a lesser extent by CYP2C19 (3). These hepatic enzyme systems mature rapidly within the first few years of postnatal life (4). There are limited pharmacokinetic data concerning racemic methadone in children, and although we might © 2012 Blackwell Publishing Ltd 1 Paediatric Anaesthesia ISSN 1155-5645