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Current guideline doses may provide suboptimal exposure in younger children. This study aims to develop a paediatric physiologically based pharmacokinetic (PBPK) model to evaluate current guidelines and propose optimized oral regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An adult PBPK model was developed and verified against 21 adult clinical studies. The model was scaled to virtual paediatric populations (0.5\u201316\u2009years old) using age\u2010dependent physiology and verified against paediatric data. Simulations assessed probability of target attainment (PTA\u2009\u2265\u200990%) for CAP (\n                      <jats:italic>f<\/jats:italic>\n                      AUC\n                      <jats:sub>ss,0\u201324<\/jats:sub>\n                      \/MIC\u2009\u2265\u200933.7) and MDR\u2010TB (\n                      <jats:italic>f<\/jats:italic>\n                      AUC\n                      <jats:sub>ss,0\u201324<\/jats:sub>\n                      \/MIC\u2009\u2265\u2009100).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The adult model was verified (test dataset geometric fold error (GMFE): 1.04; mean relative deviation [MRD]: 1.33). The scaled paediatric model accurately predicted observed concentrations (86% within 90% prediction interval). For CAP, guideline doses (10\u2009mg\/kg QD) were inadequate in children &gt;5\u2009years (PTA: 46.7%\u201363%); optimized regimens (e.g., 14\u2009mg\/kg QD for 5\u201310\u2009years) achieved PTA\u2009\u2265\u200990.4%. For MDR\u2010TB, WHO\u2010recommended doses (~15\u201320\u2009mg\/kg\/day) caused severe underexposure in children &lt;24\u2009kg (PTA: 26%\u201363%). Optimized regimens (16\u201333\u2009mg\/kg\/day) achieved PTA\u2009&gt;\u200990%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current paediatric LFX guidelines are suboptimal for CAP in children &gt;5\u2009years of age and critically inadequate for MDR\u2010TB targets in children &lt;24\u2009kg. This PBPK model provides rational, age\u2010specific oral dosing strategies to improve target attainment and support dose refinement for vulnerable paediatric populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70846","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:47:48Z","timestamp":1790326068000},"source":"Crossref","is-referenced-by-count":0,"title":["Physiologically based pharmacokinetic modelling of levofloxacin as a tool for paediatric dose optimization"],"prefix":"10.1002","author":[{"given":"Mohammad Reza","family":"Rasulzadeh","sequence":"first","affiliation":[{"name":"Student Research Committee, Faculty of Pharmacy Tabriz University of Medical Sciences  Tabriz Iran"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy Tabriz University of Medical Sciences  Tabriz 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