title: The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion.
abstract: BACKGROUND
  The optimal methadone dosing regimen for children undergoing 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 naïve adults is 58 mcg · L(-1).
  
  
  METHODS
  Adolescents aged 12-19 years undergoing idiopathic scoliosis correction were administered 0.25 mg · kg(-1) racemic methadone IV prior to surgical 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 redistribution after bolus administration. This may result in plasma concentrations that provide inadequate analgesia postoperatively. We would suggest following 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.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 800710, USA. cjs9f@virginia.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stemland
authors.forename: Jurgen
authors.initials: J
authors.lastname: Witte
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Colquhoun
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Durieux
authors.forename: Loralie J
authors.initials: LJ
authors.lastname: Langman
authors.forename: Ravi
authors.initials: R
authors.lastname: Balireddy
authors.forename: Swapna
authors.initials: S
authors.lastname: Thammishetti
authors.forename: Mark F
authors.initials: MF
authors.lastname: Abel
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D008691:Methadone / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012600:Scoliosis / Q000601:surgery*; D013123:Spinal Fusion; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone