{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:04:02Z","timestamp":1788537842687,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prof. Max Clo\u00ebtta Foundation"},{"name":"Swiss Personalized Health Network (SPHN) initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children\u2019s Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010013","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T11:24:33Z","timestamp":1703071473000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation\u2014A 10-Year Single-Center Experience"],"prefix":"10.3390","volume":"16","author":[{"given":"Katharina M.","family":"Schreib","sequence":"first","affiliation":[{"name":"Department of Stem Cell Transplantation, University Children\u2019s Hospital Zurich\u2014Eleonore Foundation & Children\u2019s Research Center (CRC), University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic S.","family":"Br\u00e4m","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike Barbara","family":"Zeilhofer","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, University Children\u2019s Hospital Zurich\u2014Eleonore Foundation & Children\u2019s Research Center (CRC), University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3261-1186","authenticated-orcid":false,"given":"Tayfun","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, University Children\u2019s Hospital Zurich\u2014Eleonore Foundation & Children\u2019s Research Center (CRC), University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-4340","authenticated-orcid":false,"given":"Stefanie D.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4618-3319","authenticated-orcid":false,"given":"Mathias M.","family":"Hauri-Hohl","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, University Children\u2019s Hospital Zurich\u2014Eleonore Foundation & Children\u2019s Research Center (CRC), University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/MOH.0000000000000289","article-title":"Haematopoietic stem cell transplantation in inborn errors of metabolism","volume":"23","author":"Chiesa","year":"2016","journal-title":"Curr. 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