SynthesisClinical pharmacokinetics2012
Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: towards individualized dosing.
Synthesis in Clinical pharmacokinetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 139 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
- Population Pharmacokinetic Model of Intravenous Busulfan in Hematopoietic Cell Transplantation: Systematic Review and Comparative Simulations.Clinical pharmacokinetics · 2023Pooled it
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Busulfan dosing algorithm and sampling strategy in stem cell transplantation patients.British journal of clinical pharmacology · 2015Trial
- Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103).Cancer chemotherapy and pharmacology · 2014Trial
- Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients.Bone marrow transplantation · 2013Trial
- Comparing the Predictive Performance of Machine Learning Models with a Newly Developed Population Pharmacokinetic Model for Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2026Article
- Updated EBMT/ESID inborn errors working party guidelines for haematopoietic stem cell transplantation for inborn errors of immunity and metabolism.Bone marrow transplantation · 2026Review
- A pilot study combining primary busulfan-based haploidentical stem cell transplantation with GD2 antibody to treat high-risk neuroblastoma.Bone marrow transplantation · 2026Article
- Busulfan pharmacokinetics in adults - a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox.Bone marrow transplantation · 2026Article
- Busulfan exposure variability and acute toxicity in pediatric patients undergoing hematopoietic stem cell gene therapy.Frontiers in pharmacology · 2026Article
- Therapeutic drug monitoring of busulfan in pediatric patients: a 5-year observational study.BMC pharmacology & toxicology · 2025Observational
- Once-Daily Versus Four-Times-Daily Intravenous Busulfan with Therapeutic Drug Monitoring as Conditioning for Hematopoietic Cell Transplantation in Children.Pharmaceutics · 2025Article
- All You Need to Know About Allometric Scaling: An Integrative Review on the Theoretical Basis, Empirical Evidence, and Application in Human Pharmacology.Clinical pharmacokinetics · 2025Review
- Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity.Blood advances · 2024Article
- Optimal Once-Daily Busulfan Administration in Pediatric Patients: A Simulation-Based Investigation of Intravenous Infusion Times.Drug design, development and therapy · 2024Article
- 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
- Vancomycin Clearance in Obese Adults is not Predictive of Clearance in Obese Adolescents.Clinical pharmacokinetics · 2023Article
- Rapid and accurate method for quantifying busulfan in plasma samples by isocratic liquid chromatography-tandem mass spectrometry (LC-MS/MS).Advances in laboratory medicine · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe wide variability in pharmacokinetics of busulfan in children is one factor influencing outcomes such as toxicity and event-free survival. A meta-analysis was conducted to describe the pharmacokinetics of busulfan in patients from 0.1 to 26 years of age, elucidate patient characteristics that explain the variability in exposure between patients and optimize dosing accordingly. PATIENTS AND
methodsData were collected from 245 consecutive patients (from 3 to 100 kg) who underwent haematopoietic stem cell transplantation (HSCT) in four participating centres. The inter-patient, inter-occasion and residual variability in the pharmacokinetics of busulfan were estimated with a population analysis using the nonlinear mixed-effects modelling software NONMEM VI. Covariates were selected on the basis of their known or theoretical relationships with busulfan pharmacokinetics and were plotted independently against the individual pharmacokinetic parameters and the weighted residuals of the model without covariates to visualize relations. Potential covariates were formally tested in the model.
resultsIn a two-compartment model, body weight was the most predictive covariate for clearance, volume of distribution and inter-compartmental clearance and explained 65%, 75% and 40% of the observed variability, respectively. The relationship between body weight and clearance was characterized best using an allometric equation with a scaling exponent that changed with body weight from 1.2 in neonates to 0.55 in young adults. This implies that an increase in body weight in neonates results in a larger increase in busulfan clearance than an increase in body weight in older children or adults. Clearance on the first day was 12% higher than that of subsequent days (p < 0.001). Inter-occasion variability on clearance was 15% between the 4 days. Based on the final pharmacokinetic-model, an individualized dosing nomogram was developed.
conclusionsThe model-based individual dosing nomogram is expected to result in predictive busulfan exposures in patients ranging between 3 and 65 kg and thereby to a safer and more effective conditioning regimen for HSCT in children.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.