ArticleBritish journal of clinical pharmacology2018
Incorporation of GSTA1 genetic variations into a population pharmacokinetic model for IV busulfan in paediatric hematopoietic stem cell transplantation.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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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.
The Therapeutic Window of Busulfan in Children With Haemopoietic Stem Cell Transplantation：A Multicenter Study in China
Implementing Pharmacogenetics in the Busulfan Dosing Method for Children Undergoing Hematopoietic Stem-cell Transplantation: a Prospective, Multicentric, Randomized Clinical Trial
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- 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
- From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2026Review
- Association of Busulfan Exposure with Event-Free Survival in a Chinese Pediatric Cohort: A Multicenter, Prospective Cohort Study.Drug design, development and therapy · 2026Observational
- Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives.Paediatric drugs · 2023Review
- Population pharmacokinetic model for once-daily intravenous busulfan in pediatric subjects describing time-associated clearance.CPT: pharmacometrics & systems pharmacology · 2022Article
- Impact of busulfan pharmacokinetics on outcome in adult patients receiving an allogeneic hematopoietic cell transplantation.Bone marrow transplantation · 2022Article
- Population Pharmacokinetics of Busulfan and Its Metabolite Sulfolane in Patients with Myelofibrosis Undergoing Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2022Article
- Effect ofPharmaceutics · 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
- Evaluation of two software using Bayesian methods for monitoring exposure and dosing once-daily intravenous busulfan in paediatric patients receiving haematopoietic stem cell transplantation.Cancer chemotherapy and pharmacology · 2021Article
- The analysis of GSTA1 promoter genetic and functional diversity of human populations.Scientific reports · 2021Article
- Optimization of Busulfan Dosing Regimen in Pediatric Patients Using a Population Pharmacokinetic Model Incorporating GST Mutations.Pharmacogenomics and personalized medicine · 2021Article
- Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2021Review
- Total Body Irradiation Forever? Optimising Chemotherapeutic Options for Irradiation-Free Conditioning for Paediatric Acute Lymphoblastic Leukaemia.Frontiers in pediatrics · 2021Review
- Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.Clinical pharmacokinetics · 2020Article
- Population pharmacokinetic analysis of intravenous busulfan: GSTA1 genotype is not a predictive factor of initial dose in Chinese adult patients undergoing hematopoietic stem cell transplantation.Cancer chemotherapy and pharmacology · 2020Article
- Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe aim of this study is to develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan metabolism.
methodsBusulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.1-20) who received intravenous busulfan during the conditioning regimen prior to stem cell transplantation. Weight, sex, baseline disease (malignant vs. non-malignant), age, conditioning regimen and GSTA1 diplotypes were evaluated as covariates of pharmacokinetic parameters by using nonlinear mixed effects analysis. The ability to achieve the target AUC
resultsA one-compartment model with first-order elimination best described the data. Allometric scaling of weight and a factor of busulfan metabolism maturation were included in the base model. GSTA1 diplotypes were found to be a significant covariate of busulfan clearance, which was 7% faster in rapid metabolizers and 12% slower in poor metabolizers, in comparison with normal ones. Busulfan doses calculated using the parameters of the proposed PopPK model were estimated to achieve the target AUC in 85.2% of the cases (95% CI 78.7-91.7%).
conclusionThis is the first PopPK for busulfan that successfully incorporated GSTA1 genotype in a paediatric population. Its use may contribute to better prediction of busulfan exposure in children and adolescents since the first dose, by tailoring the dose according to the individual metabolic capacity.
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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.