{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:48:11Z","timestamp":1789465691198,"version":"build-2803163510"},"reference-count":117,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Busulfan is a cornerstone conditioning agent for pediatric hematopoietic stem cell transplantation (HSCT), yet its narrow therapeutic index and substantial pharmacokinetic (PK) variability complicate dosing. This review synthesizes current evidence on pediatric busulfan PK, exposure-guided dosing, and the transition from conventional therapeutic drug monitoring (TDM) to model-informed precision dosing (MIPD). Methods: We conducted a focused narrative search of PubMed, Web of Science, and ScienceDirect from database inception to August 2026 and synthesized relevant literature on pediatric busulfan PK, exposure\u2013response relationships, TDM, population PK modeling, Bayesian methods, and emerging quantitative approaches. Results: Body size is the primary determinant of busulfan clearance in children, while maturation, underlying disease, concomitant medications, and pharmacogenetic variation may contribute additional variability, although their effects are inconsistent across populations. Busulfan exposure is associated with HSCT outcomes and toxicity; however, reported targets differ by dosing regimen, conditioning intensity, disease category, and exposure metric. Reliable exposure estimation requires accurate sampling records and validated bioanalysis, while limited sampling strategies may improve clinical feasibility. Integrating population PK models with Bayesian estimation enables individualized dose adjustment, although routine implementation requires external validation and compatibility with local workflows. Emerging approaches, including physiologically based PK, PK\/PD, and machine learning models, show promise but lack sufficient clinical validation for routine use. Conclusions: TDM remains the foundation of pediatric busulfan precision dosing, while MIPD provides a framework for integrating patient characteristics, measured concentrations, and validated models. Standardized workflows, population-appropriate exposure targets, prospective validation, and evidence of improved clinical outcomes are essential for broader implementation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091154","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"1154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6114-9091","authenticated-orcid":false,"given":"Xiao-Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Department of Pharmacy, Children\u2019s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China"},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Department of Pharmacy, Children\u2019s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Department of Pharmacy, Children\u2019s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Children\u2019s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan-Sheng","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-6762","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Department of Pharmacy, Children\u2019s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1182\/blood.2020009014","article-title":"Emerging approaches to improve allogeneic hematopoietic cell transplantation outcomes for nonmalignant diseases","volume":"139","author":"DeFilipp","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1016\/S2352-3026(23)00305-8","article-title":"Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: Updated recommendations by the EBMT\/ELN International Working Group","volume":"11","author":"Bacigalupo","year":"2024","journal-title":"Lancet Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108","DOI":"10.6004\/jnccn.2023.0007","article-title":"NCCN Guidelines\u00ae Insights: Hematopoietic Cell Transplantation, Version 3.2022","volume":"21","author":"Saad","year":"2023","journal-title":"J. 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