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In children, TPM dosing is body weight based. It is unknown whether children with obesity may benefit from an alternative dosing strategy. We developed a novel physiologically based pharmacokinetic (PBPK) model for TPM that accounts for age\u2010 and obesity\u2010related changes in disposition. The model was first developed and evaluated in adults before scaling to children then finally evaluated using opportunistic pharmacokinetic data from two multicenter studies where children with and without obesity ages 2\u201318 years received TPM per standard of care. Simulations were performed to characterize pharmacokinetic parameters and assess the current labeled dosing regimen in a virtual population of children with obesity (\u22652 years). The adult PBPK model performed well when evaluated with observed literature data, resulting in an average fold error of 0.989 across the dosing range of 25\u20131200 mg. The pediatric data used in model evaluation included 43 children (86% with obesity; median [range], 8 [2\u201318] years); 71% of 134 observed concentrations fell within the 90% prediction interval for the PBPK model. PBPK based dosing simulations revealed comparable exposure (&lt;20% difference) in children with and without obesity receiving the Topamax product label weight\u2010tiered dose for monotherapy (weight tiered for 2 to &lt;10 years and fixed dosing for 10 to \u226418 years) or weight\u2010based adjunctive therapy. Comparable trough concentrations between children with and without obesity suggest the current dosing recommendations, including monotherapy and adjunctive therapy, are appropriate for children with obesity.<\/jats:p>","DOI":"10.1002\/jcph.70264","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:25:38Z","timestamp":1790666738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiologically Based Pharmacokinetic Modeling to Characterize the Disposition of Topiramate in Children with and without Obesity"],"prefix":"10.1002","volume":"66","author":[{"given":"Patricia D.","family":"Maglalang","sequence":"first","affiliation":[{"name":"Eshelman School of Pharmacy, University of North Carolina  Chapel Hill 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":"Department of Medicine Duke University School of Medicine  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-2757","authenticated-orcid":false,"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. 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