{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:05:22Z","timestamp":1791227122338,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5R01HD096435"],"award-info":[{"award-number":["5R01HD096435"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HHSN275201000003I"],"award-info":[{"award-number":["HHSN275201000003I"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1T32HD104576"],"award-info":[{"award-number":["1T32HD104576"]}],"id":[{"id":"10.13039\/100009633","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":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oxcarbazepine (OXC) is a second\u2010generation antiseizure medication, effective through its active metabolite, 10\u2010mono\u2010hydroxy derivative (MHD). OXC is used as adjunctive therapy for focal\u2010onset and primary generalized tonic\u2013clonic seizures, with recommended dosing based on age and body weight. This study uses physiologically based pharmacokinetic (PBPK) modeling and leverages pharmacokinetic (PK) data acquired from children enrolled in pragmatic trials to understand dosing and subsequent exposure requirements in children with obesity. Drug concentrations of OXC and MHD (n = 148 each) from children with (n = 31) and without (n = 10) obesity, aged 2\u201020 years, were collected from two clinical trials (NCT01431326 and NCT02993861) and used for external evaluation of a previously developed PBPK model of OXC using PK\u2010Sim. We used a previously published virtual population that accounts for the obesity\u2010related changes in physiology (e.g., liver size and glomerular filtration rate) in children for PK simulations in children with obesity. Model evaluation showed that \u226580% of MHD concentrations contributed by about two thirds of study subjects (26 out of 41) fell within the 90% prediction interval. The PBPK model showed that children with obesity had lower median (interquartile range) simulated weight\u2010normalized clearance (0.060 L\/h\/kg [0.048\u20100.076 L\/h\/kg]) than children without obesity (0.067 L\/h\/kg [0.060\u20100.077 L\/h\/kg]). Simulations revealed that the recommended pediatric dosing regimen produced comparable MHD exposure between children with and without obesity at steady state, supporting its applicability regardless of obesity status. This PBPK\u2010based dosing aligns with product label recommendations and demonstrates the potential of PBPK modeling for dosing other drugs in children with obesity.<\/jats:p>","DOI":"10.1002\/jcph.70107","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T14:21:26Z","timestamp":1759155686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiologically Based Pharmacokinetic Modeling of Oxcarbazepine to Characterize Its Disposition in Children with Obesity"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-7408","authenticated-orcid":false,"given":"Patricia D.","family":"Maglalang","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2110-3370","authenticated-orcid":false,"given":"Jaydeep","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UNC School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6681-9356","authenticated-orcid":false,"given":"Vict\u1f79ria Etges","family":"Helfer","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-1653","authenticated-orcid":false,"given":"Andrea","family":"Edginton","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-6932","authenticated-orcid":false,"given":"Kanecia","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University School of Medicine  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7656-3657","authenticated-orcid":false,"given":"Chi Dang","family":"Hornik","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-0695","authenticated-orcid":false,"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago  IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7416-9755","authenticated-orcid":false,"given":"Mobeen","family":"Rathore","sequence":"additional","affiliation":[{"name":"University of Florida Center for HIV\/AIDS Research Education and Service (UF CARES)  Jacksonville FL US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0764-8585","authenticated-orcid":false,"suffix":"Jr.","given":"Daniel K.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University School of Medicine  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-5970","authenticated-orcid":false,"given":"Jia\u2010Yuh","family":"Chen","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC  Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8628-2130","authenticated-orcid":false,"given":"Ravinder","family":"Anand","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC  Rockville MD 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"}]},{"name":"the Best Pharmaceuticals for Children Act \u2013 Pediatric Trials Network Steering Committee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Novartis Pharmaceuticals Corporation.TRILEPTAL\u00ae(oxcarbazepine) film\u2010coated tablets for oral use. 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BMI. November 22 2024. Accessed March 4 2025.https:\/\/www.cdc.gov\/bmi\/child\u2010teen\u2010calculator\/bmi\u2010categories.html"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12750"},{"issue":"8","key":"e_1_2_12_21_1","first-page":"124","article-title":"In vitro\u2010in vivo evaluation of fast\u2010dissolving tablets containing solid dispersion of oxcarbazepine","volume":"8","author":"Mohan A","year":"2016","journal-title":"Int J Pharm Pharm Sci"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.14227\/DT150408P28"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.030593"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467\u2010008\u20100997\u20105"},{"key":"e_1_2_12_25_1","unstructured":"Open\u2010Systems\u2010Pharmacology.PK\u2010Sim Ontogeny Database. 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