{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T14:50:55Z","timestamp":1769352655391,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,9,14]],"date-time":"2012-09-14T00:00:00Z","timestamp":1347580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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 na\u00efve adults is 58\u00a0mcg\u00b7L<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adolescents aged 12\u201319\u00a0years undergoing idiopathic scoliosis correction were administered 0.25\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> racemic methadone <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> prior to surgical incision. Arterial blood samples for methadone assay were obtained at 0\u00a0min, 5\u00a0min, 10\u00a0min, 15\u00a0min, 20\u00a0min, 40\u00a0min, 1\u00a0h, 2\u00a0h, 4\u00a0h, 5\u00a0h, 6\u00a0h, 8\u00a0h, 10\u00a0h, 12\u00a0h, 24\u00a0h, and 48\u00a0h. Compartment analysis was undertaken using nonlinear mixed effects models. Parameter estimates were standardized to a 70\u2010kg person using allometric models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A three\u2010compartment linear disposition model best described observed time\u2013concentration profiles. Population parameter estimates (between\u2010subjects variability) were central volume (V1) 19.1 (126%) L 70\u00a0kg<jats:sup>\u22121<\/jats:sup>, peripheral volumes of distribution V2 65.5 (60%) L 70\u00a0kg<jats:sup>\u22121<\/jats:sup>, V3 485 (23%) L 70\u00a0kg<jats:sup>\u22121<\/jats:sup>, clearance (<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>) 9.3 (11%) L\u00b7h<jats:sup>\u22121<\/jats:sup>\u00b770\u00a0kg<jats:sup>\u22121<\/jats:sup>, and inter\u2010compartment clearances Q2 282 (95%) L\u00b7h<jats:sup>\u22121<\/jats:sup> 70\u00a0kg<jats:sup>\u22121<\/jats:sup>, Q3 139 (42%) L\u00b7h<jats:sup>\u22121<\/jats:sup> 70\u00a0kg<jats:sup>\u22121<\/jats:sup>. The terminal elimination half\u2010life was 44.4\u00a0h. The mean observed methadone concentration was &lt;58\u00a0mcg\u00b7L<jats:sup>\u22121<\/jats:sup> by the first hour after administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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<jats:sup>\u20101<\/jats:sup>) with an infusion (0.1\u20130.15\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup> for 4 h) during spinal surgery to ensure adequate plasma concentrations for 24\u00a0h.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.12021","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T05:05:46Z","timestamp":1347685546000},"page":"51-57","source":"Crossref","is-referenced-by-count":48,"title":["The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion"],"prefix":"10.1111","volume":"23","author":[{"given":"Christopher J.","family":"Stemland","sequence":"first","affiliation":[{"name":"Department of Anesthesiology University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Intensive Care and Pain Medicine, University Hospital Munster Munster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas A.","family":"Colquhoun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel E.","family":"Durieux","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loralie J.","family":"Langman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Balireddy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swapna","family":"Thammishetti","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark F.","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3181d8a095"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)81054-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.05.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198212000-00005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198407000-00005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238fec5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198709001-00519"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.128386"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00542102"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1987.47"},{"key":"e_1_2_8_13_1","volume-title":"NONMEM Users Guides. 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