{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:18Z","timestamp":1787567778101,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Methadone is used in hospitalized children to treat pain and iatrogenic opiate withdrawal. Optimal pediatric dosing for both enteral and intravenous methadone is unknown. We conducted two prospective, multi\u2010center, open\u2010label studies to characterize the pharmacokinetics of methadone in the pediatric population. These studies were conducted at a total of 23 US children's hospitals. Ninety\u2010nine children with a median (range) age of 2.3 (0\u201319.0) years and weight of 13.0 (0.72\u2013159) kg were prescribed methadone per standard of care for treatment of pain or iatrogenic opiate withdrawal. Ninety\u2010nine children received median (range) methadone doses of 0.11 (0.01\u20130.39) mg\/kg intravenously and 0.10 (0.01\u20130.61) mg\/kg enterally. Ten participants received only intravenous doses; 78 received only enteral doses; and 11 received intravenous and enteral doses. We analyzed 263 pharmacokinetic samples with a median (range) methadone plasma concentration of 42.2 (0.9\u2013729.2) ng\/mL. A one\u2010compartment population pharmacokinetic model described the methadone data well. Median (range) empiric Bayesian estimates of clearance, volume of distribution, and half\u2010life were 0.17 (0.009\u20131.50) L\/h\/kg, 4.99 (0.97\u201320.6) L\/kg, and 20.5 (3.0\u201386.2) h, respectively. Dosing simulations showed that doses of 0.1 mg\/kg every 8 h (intravenous) and 0.2 mg\/kg every 8 h (enteral) achieved exposures associated with pain control and reduction in withdrawal symptoms. Based on observed exposures and model simulations, we recommend a starting dose of 0.1 mg\/kg intravenous or 0.2 mg\/kg enterally (max 10 mg) every 8 h. Because of wide interindividual variability, this dose should be titrated to effect.<\/jats:p>","DOI":"10.1002\/jcph.70143","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:59:36Z","timestamp":1767185976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Population Pharmacokinetics to Support Intravenous and Enteral Methadone Dosing in Children"],"prefix":"10.1002","volume":"66","author":[{"given":"Kevin M.","family":"Watt","sequence":"first","affiliation":[{"name":"University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-1789","authenticated-orcid":false,"given":"Elizabeth J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Lam","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanecia","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Atz","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina  Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Johns Hopkins All Children's Hospital  St. Petersburg FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Hupp","sequence":"additional","affiliation":[{"name":"Emory University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Bhatt\u2010Mehta","sequence":"additional","affiliation":[{"name":"University of Michigan Medical Center  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Daniel K.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Anand","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cohen\u2010Wolkowiez","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5522-5686","authenticated-orcid":false,"given":"Daniel","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute  Durham NC USA"},{"name":"Division of Clinical Pharmacology Department of Medicine Duke University School of Medicine  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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