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Enoxaparin, a commonly prescribed low\u2010molecular\u2010weight heparin, is dosed based on body weight irrespective of obesity status to achieve maximum concentration within a narrow therapeutic or prophylactic target range. However, whether children with and without obesity experience equivalent enoxaparin exposure remains unclear. To address this clinical question, 2,825 anti\u2013activated factor X (anti\u2010Xa) surrogate concentrations were collected from the electronic health records of 596 children, including those with obesity. Using linear mixed\u2010effects regression models, we observed that 4\u2010hour anti\u2010Xa concentrations were statistically significantly different in children with and without obesity, even for children with the same absolute dose (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004). To further mechanistically explore obesity\u2010associated differences in anti\u2010Xa concentration, a pediatric physiologically\u2010based pharmacokinetic (PBPK) model was developed in adults, and then scaled to children with and without obesity. This PBPK model incorporated binding of enoxaparin to antithrombin to form anti\u2010Xa and elimination via heparinase\u2010mediated metabolism and glomerular filtration. Following scaling, the PBPK model predicted real\u2010world pediatric concentrations well, with an average fold error (standard deviation of the fold error) of 0.82 (0.23) and 0.87 (0.26) in children with and without obesity, respectively. PBPK model simulations revealed that children with obesity have at most 20% higher 4\u2010hour anti\u2010Xa concentrations under recommended, total body weight\u2013based dosing compared to children without obesity owing to reduced weight\u2010normalized clearance. Enoxaparin exposure was better matched across age groups and obesity status using fat\u2010free mass weight\u2010based dosing.<\/jats:p>","DOI":"10.1002\/cpt.2618","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T07:44:00Z","timestamp":1650613440000},"page":"391-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Use of Real\u2010World Data and Physiologically\u2010Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4679-4638","authenticated-orcid":false,"given":"Jacqueline G.","family":"Gerhart","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina Eshelman School of Pharmacy The University of North Carolina at Chapel Hill  Chapel Hill North Carolina 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University of North Carolina School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-6350","authenticated-orcid":false,"given":"Karan R.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute  Durham North Carolina USA"},{"name":"Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-1534","authenticated-orcid":false,"given":"Carl M.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Centre for Medicine Use and Safety Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-8759","authenticated-orcid":false,"given":"Christoph 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