ArticleScientific reports2017
Pharmacometabolomics for predicting variable busulfan exposure in paediatric haematopoietic stem cell transplantation patients.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- From Therapeutic Drug Monitoring to Model-Informed Precision Dosing: A Review of Busulfan Dosing Optimization in Pediatric Hematopoietic Stem Cell Transplantation.Pharmaceutics · 2026Review
- Population Pharmacokinetics of Melphalan in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation with Various Conditioning Regimens.European journal of drug metabolism and pharmacokinetics · 2026Article
- Pioglitazone-induced alterations of purine metabolism in healthy male subjects.Clinical and translational science · 2024Article
- Metabolomics: A Tool to Envisage Biomarkers in Clinical Interpretation of Cancer.Current drug research reviews · 2024Review
- Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling.Clinical pharmacology and therapeutics · 2023Article
- Population pharmacokinetic model for once-daily intravenous busulfan in pediatric subjects describing time-associated clearance.CPT: pharmacometrics & systems pharmacology · 2022Article
- Dietary Goji Shapes the Gut Microbiota to Prevent the Liver Injury Induced by Acute Alcohol Intake.Frontiers in nutrition · 2022Article
- Urinary Metabolomic Profiling after Administration of Corydalis Tuber and Pharbitis Seed Extract in Healthy Korean Volunteers.Pharmaceutics · 2021Article
- Review of the Pharmacokinetics and Pharmacodynamics of Intravenous Busulfan in Paediatric Patients.Clinical pharmacokinetics · 2021Review
- Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.Clinical pharmacokinetics · 2020Article
- Metabolomics technology and bioinformatics for precision medicine.Briefings in bioinformatics · 2019Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups. In the high-AUC group, deferoxamine metabolites were detected. Phenylacetylglutamine and two acylcarnitines were significantly lower in the high-AUC group than in the low-AUC group. Deferoxamine, an iron-chelating agent that lowers serum ferritin levels, was detected in the high-AUC group, indicating that those patients had high ferritin levels. Therefore, in a retrospective study of 130 paediatric patients, we confirmed our hypothesis that busulfan clearance (dose/AUC) and serum ferritin level has a negative correlation (r = -0.205, P = 0.019). Ferritin, acylcarnitine, and phenylacetylglutamine are associated with liver damage, including free radical formation, deregulation of hepatic mitochondrial β-oxidation, and hyperammonaemia. Our findings reveal potential biomarkers predictive of busulfan exposure and suggest that liver function may affect busulfan exposure.
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