{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:15:59Z","timestamp":1790363759304,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007546"],"award-info":[{"award-number":["T32GM007546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Each year 25 000\u201332 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR\/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR\/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)\u2013recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101\u2005mg\u00b7h\/L given current standard adult doses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Data from 242 children (2.8 years [0.2\u201316.8] was used). Apparent clearance was 3.16 L\/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing &amp;lt;24\u2005kg and under &amp;lt;10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16\u201333\u2005mg\/kg for dispersible tablets or 16\u201350\u2005mg\/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Revised weight-band dosing guidelines with doses of &amp;gt;20\u2005mg\/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae024","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T14:17:30Z","timestamp":1707574650000},"page":"756-764","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis"],"prefix":"10.1093","volume":"78","author":[{"given":"Yasmine N","family":"White","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutics, Schools of Pharmacy and Medicine, University of California\u2013San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-5480","authenticated-orcid":false,"given":"Belen P","family":"Solans","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutics, Schools of Pharmacy and Medicine, University of California\u2013San Francisco , San Francisco, California , USA"},{"name":"Center for Tuberculosis, University of California\u2013San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louvina E","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town , South Africa"},{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape 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