{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T16:45:39Z","timestamp":1768841139293,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Severe coronavirus disease 2019 (COVID\u201019) disease, including multisystem inflammatory syndrome, has been reported in children. This report summarizes development of a remdesivir physiologically\u2010based pharmacokinetic (PBPK) model that accurately describes observed adult remdesivir and metabolites exposure and predicts pediatric remdesivir and metabolites exposure. The adult PBPK model was applied to predict pediatric remdesivir and metabolites steady\u2010state exposures using the Pediatric Population Model in SimCYP and incorporated the relevant physiologic and mechanistic information. Model development was based on adult phase I exposure data in healthy volunteers who were administered a 200\u2010mg loading dose of remdesivir intravenous (IV) over 0.5\u00a0hours on Day 1, then 100\u2010mg daily maintenance doses of IV over 0.5\u00a0hours starting on Day 2 and continuing through Days 5 or 10. Simulations indicated that use of the adult therapeutic remdesivir dosage regimen (200\u2010mg loading dose on Day 1 then 100\u2010mg daily maintenance dose starting on Day 2) in pediatric patients\u00a0\u2265\u00a040\u00a0kg and a weight\u2010based remdesivir dosage regimen (5\u2010mg\/kg loading dose on Day 1 then 2.5\u2010mg\/kg daily maintenance dose starting on Day 2) in pediatric patients weighing 2.5 to &lt; 40\u00a0kg is predicted to maintain therapeutic exposures of remdesivir and its metabolites. The comprehensive PBPK model described in this report supported remdesivir dosing in planned pediatric clinical studies and dosing in the emergency use authorization and pediatric compassionate use programs that were initiated to support remdesivir as a treatment option during the pandemic.<\/jats:p>","DOI":"10.1002\/cpt.2176","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T13:10:28Z","timestamp":1611753028000},"page":"1116-1124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Physiologically\u2010Based Pharmacokinetic Modeling of Remdesivir and Its Metabolites to Support Dose Selection for the Treatment of Pediatric Patients With COVID\u201019"],"prefix":"10.1111","volume":"109","author":[{"given":"Justin D.","family":"Lutz","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Gilead Sciences Inc. 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