ArticleClinical pharmacokinetics2020
Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.
Article in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- A practical guide to therapeutic drug monitoring in busulfan: recommendations from the Pharmacist Committee of the European Society for Blood and Marrow Transplantation (EBMT).Bone marrow transplantation · 2024Guideline
- From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2026Review
- Simulation-Based Evaluation of Busulfan Sampling Strategies in Adults and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.Journal of clinical pharmacology · 2026Article
- Busulfan pharmacokinetics in adults - a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox.Bone marrow transplantation · 2026Article
- Impact of busulfan exposure stratification on transplant outcomes and immune reconstitution in children with severe aplastic anemia.Frontiers in pharmacology · 2026Article
- Association of Busulfan Exposure with Event-Free Survival in a Chinese Pediatric Cohort: A Multicenter, Prospective Cohort Study.Drug design, development and therapy · 2026Observational
- [Effect of phenytoin and levetiracetam on busulfan blood concentration in children undergoing hematopoietic stem cell transplantation].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Dosing chemotherapy in children with obesity: literature review and evaluation of local practices.Cancer chemotherapy and pharmacology · 2025Review
- Review
- Adaptive dosing of high-dose busulfan in real-world adult patients undergoing haematopoietic cell transplant conditioning.British journal of clinical pharmacology · 2025Article
- A limited sampling strategy for estimating busulfan exposure in pediatric hematopoietic stem cell transplantation.Frontiers in pharmacology · 2025Article
- Article
- Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen.Bone marrow transplantation · 2023Observational
- Precision Oncology by Point-of-Care Therapeutic Drug Monitoring and Dosage Adjustment of Conventional Cytotoxic Chemotherapies: A Perspective.Pharmaceutics · 2023Review
- Population Pharmacokinetics of Busulfan and Its Metabolite Sulfolane in Patients with Myelofibrosis Undergoing Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2022Article
- Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?Frontiers in pediatrics · 2022Article
- External Evaluation of Population Pharmacokinetic Models of Busulfan in Chinese Adult Hematopoietic Stem Cell Transplantation Recipients.Frontiers in pharmacology · 2022Article
- The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study.Frontiers in pharmacology · 2022Article
- Evaluation of the Robustness of Therapeutic Drug Monitoring Coupled with Bayesian Forecasting of Busulfan with Regard to Inaccurate Documentation.Pharmaceutical research · 2021Article
- Precision dosing of intravenous busulfan in pediatric hematopoietic stem cell transplantation: Results from a multicenter population pharmacokinetic study.CPT: pharmacometrics & systems pharmacology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBusulfan therapeutic drug monitoring (TDM) is necessary to better achieve the target exposure in children before hematopoietic stem cell transplantation (HSCT). However, TDM-based dosing may be challenging if intra-individual pharmacokinetic variability (also denoted inter-occasion variability [IOV]) occurs during therapy.
objectivesThe objectives of this study were to describe and quantify busulfan IOV in children, and to investigate its potential determinants.
methodsWe performed a new analysis of published data from children who received intravenous busulfan over 4 days before HSCT. We calculated individual pharmacokinetic parameters on each day of therapy using a published population pharmacokinetic model of busulfan and analyzed their changes. Population estimation of IOV was also performed with non-linear mixed effects (NLME) modeling. Potential predictors of significant decrease in busulfan clearance (CL) were assessed by using machine learning approaches.
resultsIOV could be assessed in 136 children. Between day (D) 1 and D2, most patients (80%) experienced a decrease in busulfan CL, with a median change of - 7.9%. However, both large decreases (minimum, - 48.5%) and increases in CL (maximum, + 44%) were observed. Over D1-D3 of therapy, mean CL significantly decreased (- 15%), with a decrease of ≥ 20% in 22% of patients. Some patients also showed unstable CL from day to day. NLME modeling of IOV provided a coefficient of variation of 10.6% and 13.1% for volume of distribution (V
conclusionsSignificant busulfan intra-individual variability may occur in children who receive a HSCT and is hardly predictable. The main risk is busulfan overexposure. Performing TDM repeatedly over therapy appears to be the best way to accurately estimate busulfan exposure and perform precision dosing.
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