Trial reportClinical pharmacokinetics2015
Age-Dependent Pharmacokinetics of Doxorubicin in Children with Cancer.
Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Towards a Model-Based Dose Recommendation for Doxorubicin in Children.Clinical pharmacokinetics · 2017Trial
- Pharmacokinetic and pharmacodynamic study of doxorubicin in children with cancer: results of a "European Pediatric Oncology Off-patents Medicines Consortium" trial.Cancer chemotherapy and pharmacology · 2016Trial
- A Population Pharmacokinetic Study to Evaluate Doxorubicin Exposure Across All Age Groups.Clinical pharmacokinetics · 2024Article
- Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial.Cancer chemotherapy and pharmacology · 2024Article
- Pediatric Cardio-Oncology: Screening, Risk Stratification, and Prevention of Cardiotoxicity Associated with Anthracyclines.Children (Basel, Switzerland) · 2024Review
- The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children's Oncology Group and NRG Oncology study ARST1321.Cancer chemotherapy and pharmacology · 2022Article
- Chemotherapy induced damage to spermatogonial stem cells in prepubertal mouse in vitro impairs long-term spermatogenesis.Toxicology reports · 2021Article
- Subclinical doxorubicin-induced cardiotoxicity update: role of neutrophils and endothelium.American journal of cancer research · 2021Review
- Can we optimise doxorubicin treatment regimens for children with cancer? Pharmacokinetic simulations and a Delphi consensus procedure.BMC pharmacology & toxicology · 2020Article
- Role of Endothelium in Doxorubicin-Induced Cardiomyopathy.JACC. Basic to translational science · 2018Review
- Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non-Hodgkin's lymphoma.British journal of clinical pharmacology · 2016Article
- How to Improve the Safe and Effective Use of Doxorubicin in Children with Cancer.Clinical pharmacokinetics · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveKnowledge on the pharmacokinetics of doxorubicin, especially in children, is very limited with conflicting evidence concerning a possible age dependency in the pharmacokinetics. The aim of the current investigation was to assess, by using population pharmacokinetics, whether an age dependency in the clearance (CL) of doxorubicin exists.
methodsPharmacokinetic data of doxorubicin and its main metabolite doxorubicinol from 94 children (aged 0-18 years) from the EPOC-MS-001-Doxo trial were available. A population pharmacokinetic model was developed in NONMEM(®) 7.2.0.
resultsA linear three-compartment model for doxorubicin, with one additional compartment for doxorubicinol, gave the best fit to the data. All model parameters were linearly scaled on body surface area. Including a power function of age as a covariate for CL led to a further improvement of the model. Variation in genes encoding for enzymes involved in the metabolism or active transport of doxorubicin had no influence on the pharmacokinetics. Estimates of CL were lower (26.6 L/h/m(2) in children aged >3 years and 21.1 L/h/m(2) in children aged ≤3 years, p = 0.0004) in children aged <3 years, compared with older children.
conclusionsThis is the first model to describe the pharmacokinetics of doxorubicin in children, with a specific focus on infants and children aged <3 years. The lower CL in younger children should be considered together with the pharmacodynamics, especially the cardiotoxicity, when selecting the dose for future protocols.
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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.