ArticleEuropean journal of clinical pharmacology2024
The impact of age and renal function on the pharmacokinetics and protein binding characteristics of fludarabine in paediatric and adult patients undergoing allogeneic haematopoietic stem cell transplantation conditioning.
Article in European journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inclusion, characteristics, and reporting of older patients in recent registration trials for DLBCL.Blood advances · 2026Pooled it
- Impact of fludarabine exposure on CAR T-cell outcomes in patients with large B-cell lymphoma.Blood advances · 2026Article
- Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Fludarabine dosing in the youngest children: safety first.Blood advances · 2026Article
- Article
- Cellular pharmacology of fludarabine: molecular determinants of transport and metabolism.Frontiers in pharmacology · 2026Review
- Towards Personalized Lymphodepletion: A Population Pharmacokinetic Fludarabine Model in Patients Receiving CAR T-Cell Therapy.Pharmaceutics · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
aimTo evaluate the population pharmacokinetics of unbound F-Ara-A (the circulating metabolite of fludarabine) in 211 patients (age range, 0.1-63.4 years) undergoing allogeneic haematopoietic stem cell transplantation conditioning.
methodsTotal (n = 2480) and unbound (n = 1403) F-Ara-A concentrations were measured in blood samples collected at timed intervals after fludarabine doses ranging from 10 to 50 mg/m
resultsThe base population mean estimates ± relative standard error (%RSE) for unbound clearance from the central compartment (CLu) and inter-compartmental clearances (Q2u, Q3u) were 3.42 ± 3%, 6.54 ± 24% and 1.47 ± 16% L/h/70 kg, respectively. The population mean estimates (%RSE) for the unbound volume of distribution into the central (V1u) and peripheral compartments (V2u, V3u) were 9.65 ± 8%, 8.17 ± 9% and 16.4 ± 10% L/70 kg, respectively, and that for fu was 0.877 ± 1%. Covariate model development involved differentiating F-Ara-A CLu into non-renal (1.81 ± 9% L/h/70 kg) and renal components (1.02 ± 9%*GFR L/h/70 kg). A sigmoidal maturation factor was applied to renal CLu, with population mean estimates for the Hill exponent and PMA at 50% mature of 2.97 ± 4% and 69.1 ± 8% weeks, respectively.
conclusionPatient age and GFR are predictors of unbound F-Ara-A CLu. This has the potential to impact dose requirements. Dose individualisation by target concentration intervention will be facilitated by this model once it is externally validated.
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