{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:26:01Z","timestamp":1793039161267,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","award":["Center of Excellence in Drug Development and Clinical Pharmacology"],"award-info":[{"award-number":["Center of Excellence in Drug Development and Clinical Pharmacology"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>Apply population pharmacokinetic modeling to a single institution busulfan therapeutic drug monitoring (TDM) data set from infants and children to refine dosing methods.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>One-compartment pharmacokinetic model was fit to busulfan TDM data from 328 infants and children with malignant and non-malignant diseases treated with busulfan-containing transplant conditioning regimens. Age-dependence of busulfan clearance scaled to body weight and body surface area (BSA) was compared, and busulfan AUC was simulated for a BSA-scaled dose of 100 mg\/m<jats:sup>2<\/jats:sup> combined with a BSA-banded dosing table for infants and children with a BSA\u2009&lt;\u20090.5 m<jats:sup>2<\/jats:sup>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Busulfan clearance scaled to body weight is age-dependent. Clearance in children\u2009\u2264\u20093 years (0.234\u00a0L\/[h\u2022kg]) is higher than the typical value for the population, (0.205\u00a0L\/[h\u2022kg]), and 48% of children\u2009&lt;\u20095 years have subtherapeutic busulfan AUCs after the first dose. Busulfan clearance scaled to BSA (typical value, 5.47\u00a0L\/[h\u2022m<jats:sup>2<\/jats:sup>]) is more uniform across the pediatric age span, except for infants (\u2264\u20091 year, 4.27\u00a0L\/[h\u2022m<jats:sup>2<\/jats:sup>]). Simulated busulfan AUCs with a dose of 100 mg\/m<jats:sup>2<\/jats:sup> for patients with a BSA\u2009\u2265\u20090.5 m<jats:sup>2<\/jats:sup> combined with a BSA-banded dosing table for patients with a BSA\u2009&lt;\u20090.5 m<jats:sup>2<\/jats:sup> achieved a therapeutic AUC after the first dose in 49% more patients than body weight scaled doses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our model predicts a greater proportion of children would achieve a therapeutic busulfan <jats:italic>AUC<\/jats:italic> after the first dose with a dose of 100 mg\/m<jats:sup>2<\/jats:sup>\/d combined with the infant dosing table for patients with a BSA\u2009&lt;\u20090.5 m<jats:sup>2<\/jats:sup> compared to body weight-scaled dosing.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00280-025-04757-w","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T15:03:46Z","timestamp":1739286226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis"],"prefix":"10.1007","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-6926","authenticated-orcid":false,"given":"Frank M.","family":"Balis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Bunin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Gardiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Milone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"issue":"11","key":"4757_CR1","doi-asserted-by":"publisher","first-page":"e526","DOI":"10.1016\/S2352-3026(16)30114-4","volume":"3","author":"IH Bartelink","year":"2016","unstructured":"Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Theoret Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Gungor T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ (2016) Association of Busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. 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