{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:22:18Z","timestamp":1779927738597,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HHSN275201000003I"],"award-info":[{"award-number":["HHSN275201000003I"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HHSN275201800003I"],"award-info":[{"award-number":["HHSN275201800003I"]}],"id":[{"id":"10.13039\/100000071","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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diazepam is a benzodiazepine approved for use in adults and children. The label incorporates recommended dosing for status epilepticus in children. Published population pharmacokinetic (PK) modeling recommends an intravenous bolus dose of 0.2 mg\/kg capped at 8 mg to reach the suggested target exposure of 200\u2010600 ng\/mL at 10 min post dose in children up to 17 years of age. This model was developed for children generally without obesity based on IV data, and it is unclear how increased body weight may affect exposure or target attainment given capped dosing. Diazepam concentrations after IV or oral administration for 61 children aged 2.5 to 20.6 years were used to externally evaluate the model including the addition of fixed oral absorption parameters. Then, PK parameters were re\u2010estimated with the external population alone and again in combination with the original population. Re\u2010estimated parameters from the combined population were used to simulate recommended dosing for children with and without obesity. The external dataset included 88 plasma concentrations from 61 children (54 with obesity) receiving diazepam per standard of care. The external evaluation resulted in 34.5% of predicted values within 30% of the observed concentration. Parameter re\u2010estimation resulted in increased central volume of distribution (26% increase from a previous model), reduced peripheral volume of distribution and intercompartmental clearance, and similar clearance estimates. Simulations demonstrated that dosing caps may prevent children with obesity from reaching the suggested target exposure that is recommended for the treatment of status epilepticus. Further study is needed to evaluate the target exposure range in this population.<\/jats:p>","DOI":"10.1002\/jcph.70027","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T03:14:56Z","timestamp":1745810096000},"page":"1135-1149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expansion of a Pharmacokinetic Model for Diazepam to Characterize Real\u2010World IV and Oral Data in Children With and Without Obesity"],"prefix":"10.1002","volume":"65","author":[{"given":"Sean M.","family":"McCann","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 North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-9665","authenticated-orcid":false,"given":"Jiali","family":"Wen","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 North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-1680","authenticated-orcid":false,"given":"Stephen J.","family":"Balevic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"},{"name":"Duke Clinical Research Institute  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Ann and Robert H. 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