{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:20:30Z","timestamp":1792246830923,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018896","name":"Kids Cancer Alliance","doi-asserted-by":"publisher","award":["15\/TRC\/1\u201004"],"award-info":[{"award-number":["15\/TRC\/1\u201004"]}],"id":[{"id":"10.13039\/501100018896","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the pharmacokinetics (PK) of intravenous treosulfan in paediatric patients undergoing haematopoietic stem cell transplantation (HSCT) for a broad range of diseases and to explore the impact of different dosing regimens on treosulfan exposure (area under the concentration\u2013time curve, AUC<jats:sub>0\u2192\u221e<\/jats:sub>) through dosing simulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective multicentre PK study was conducted using treosulfan concentration data (<jats:italic>n<\/jats:italic>\u2009=\u2009423) collected from 53 children (median age 3.5, range 0.2\u201317.0\u00a0years) receiving three daily age\u2010guided doses (10\u201314\u2009g\/m<jats:sup>2<\/jats:sup>). Population PK modelling was performed using NONMEM software, utilising a stepwise forward selection backward elimination method and likelihood\u2010ratio test for screening covariates to describe PK variability. Monte Carlo simulation was used to generate patient PK data for 10\u2009000 virtual paediatric patients and cumulative AUC<jats:sub>0\u2192\u221e<\/jats:sub> values were evaluated using age, body surface area (BSA) and model\u2010based dosing regimens, targeting 4800\u2009mg*h\/L.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treosulfan concentration data were described using a one\u2010compartment PK model with first\u2010order elimination. Population mean (95% CI) estimates for clearance (CL) and volume of distribution (V) were 16.3 (14.9\u201318.1) L\/h and 41.9 (38.8\u201345.1) L, respectively. Allometrically scaled body weight was the best covariate descriptor for CL and V, and maturational age further explained variability in CL. Dosing simulations indicated that in young patient groups (&lt;2\u00a0years), a model\u2010based dosing regimen more accurately achieved the target AUC<jats:sub>0\u2192\u221e<\/jats:sub> (58.3%) over the age (42.6%) and BSA\u2010based (51.3%) regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treosulfan disposition was described through allometric body weight and maturational age descriptors. Model\u2010informed dosing is recommended for patients under 2\u00a0years. Treosulfan PK parameters and AUC<jats:sub>0\u2192\u221e<\/jats:sub> were not influenced by patient disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15599","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T05:43:10Z","timestamp":1668231790000},"page":"1413-1424","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of treosulfan cumulative exposure in paediatric patients through population pharmacokinetics and dosing simulations"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-4904","authenticated-orcid":false,"given":"Sebastian P. 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