ArticleBritish journal of clinical pharmacology2020
A semi-mechanistic model based on glutathione depletion to describe intra-individual reduction in busulfan clearance.
Article in British journal of clinical pharmacology, 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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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, 28 citations in OpenAlex.
- Population Pharmacokinetic Model of Intravenous Busulfan in Hematopoietic Cell Transplantation: Systematic Review and Comparative Simulations.Clinical pharmacokinetics · 2023Pooled it
- Effects of combined test dose and therapeutic drug monitoring strategy in exposure-directed busulfan.Annals of hematology · 2023Trial
- αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies.Blood advances · 2021Trial
- Comparing the Predictive Performance of Machine Learning Models with a Newly Developed Population Pharmacokinetic Model for Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2026Article
- From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2026Review
- Clinical Impact of Maximum Plasma Concentration of Busulfan in Pediatric Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation.Clinical pharmacology and therapeutics · 2026Article
- Busulfan pharmacokinetics in adults - a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox.Bone marrow transplantation · 2026Article
- Risk factors for alloimmune lung syndromes after allogeneic hematopoietic cell transplantation in children.Bone marrow transplantation · 2026Article
- Model-Informed Precision Dosing of Busulfan for Children and Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Critical Evaluation of Current PK Models and Dose Recommendations.Clinical pharmacology and therapeutics · 2025Article
- Adaptive dosing of high-dose busulfan in real-world adult patients undergoing haematopoietic cell transplant conditioning.British journal of clinical pharmacology · 2025Article
- Semi-mechanistic population pharmacokinetic model incorporating glutathione S-transferase activity for personalized busulfan dosing in pediatric allogeneic hematopoietic cell transplantation.Frontiers in pharmacology · 2025Article
- Maximum a posteriori Bayesian methods out-perform non-compartmental analysis for busulfan precision dosing.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Article
- Lymphodepletion - an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle.Frontiers in immunology · 2023Review
- Population pharmacokinetic model for once-daily intravenous busulfan in pediatric subjects describing time-associated clearance.CPT: pharmacometrics & systems pharmacology · 2022Article
- Review
- 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
- Precision dosing of intravenous busulfan in pediatric hematopoietic stem cell transplantation: Results from a multicenter population pharmacokinetic study.CPT: pharmacometrics & systems pharmacology · 2021Article
- Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust.HemaSphere · 2021Review
- Total Body Irradiation Forever? Optimising Chemotherapeutic Options for Irradiation-Free Conditioning for Paediatric Acute Lymphoblastic Leukaemia.Frontiers in pediatrics · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
aimTo develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing.
methodsBusulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a semi-mechanistic model and compare it to a previously developed empirical model. The latter included an empirically estimated time effect, where the semi-mechanistic model included theoretical glutathione depletion. As older age has been related to lower glutathione levels, this was tested as a covariate in the semi-mechanistic model. Lastly, a therapeutic drug monitoring (TDM) simulation was performed comparing the two models in target attainment.
resultsIn both models, a similar clearance decrease of 7% (range -82% to 44%), with a proportionality to busulfan metabolism, was found. After 40 years of age, the time effect increased with 4% per year of age (0.6-8%, P = 0.009), causing the effect to increase more than a 2-fold over the observed age-range (0-73 years). Compared to the empirical model, the final semi-mechanistic model increased target attainment from 74% to 76%, mainly through better predictions for adult patients.
conclusionThese results suggest that the time-dependent decrease in busulfan clearance may be related to gluthathione depletion. This effect increased with older age (>40 years) and was proportional to busulfan metabolism. The newly constructed semi-mechanistic model could be used to further improve TDM-guided exposure target attainment of busulfan in patients undergoing HCT.
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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.