{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:03:27Z","timestamp":1772118207173,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The European Society for Blood and Marrow Transplantation (EBMT) recommends a busulfan target cumulative area under the curve (cAUC) of 78\u2013101\u00a0mg\u00b7h\/L for hematopoietic stem cell transplantation (HSCT). Currently, no population pharmacokinetic (PopPK)\u2010optimized four\u2010times\u2010daily (Q6H) regimen reliably achieves this range. We developed a PopPK\u2010guided dosing protocol to address this gap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and demographic data from pediatric HSCT recipients receiving busulfan were retrospectively analyzed to develop a PopPK model. Bayesian estimation identified the optimal busulfan dose (0.50\u20131.25\u00a0mg\/kg\/dose) for target attainment in pediatric patients (age 0.5\u201318\u00a0years; weight 5\u201380\u00a0kg). Finally, the proposed dosing strategy was validated using an independent retrospective cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PopPK model was developed using data from 65 pediatric patients. Age and bodyweight were identified as significant covariates. Optimized dosing recommendations for the Q6H \u00d7 4\u00a0days busulfan regimen were established through Bayesian estimation. For validation, two cohorts were retrospectively analyzed: (i) weight\u2010based dosing (<jats:italic>n<\/jats:italic> = 19), and (ii) model\u2010informed dosing (<jats:italic>n<\/jats:italic> = 15). The groups demonstrated comparable distributions in both age (<jats:italic>p<\/jats:italic> = 0.78) and weight (<jats:italic>p<\/jats:italic> = 0.63). Notably, the model\u2010informed group achieved significantly higher cAUC values (mean difference, 18.0\u00a0mg\u00b7h\/L; 95% confidence interval: 9.83\u201326.1\u00a0mg\u00b7h\/L; <jats:italic>p<\/jats:italic> &lt; 0.001), with 67% of these patients reaching the target exposure range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We developed a Q6H \u00d7 4\u00a0days busulfan dosing regimen through PopPK modeling. For a representative 6\u2010year\u2010old patient with a bodyweight of 20\u00a0kg, the recommended dose is 1.25\u00a0mg\/kg\/dose. Therapeutic drug monitoring following the initial dose remains clinically essential.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31969","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T06:20:26Z","timestamp":1754720426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Population Pharmacokinetics of Busulfan in Pediatric Patients: Optimization of a Four\u2010Times\u2010Daily Dosing Regimen Based on EBMT Recommendations"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1709-9631","authenticated-orcid":false,"given":"Zeyuan","family":"He","sequence":"first","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiebin","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"wu","family":"Junyan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou 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