ArticleBritish journal of clinical pharmacology2017
Population pharmacokinetics of temsirolimus and sirolimus in children with recurrent solid tumours: a report from the Children's Oncology Group.
Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.International journal of molecular sciences · 2021Pooled it
- The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.Current pharmaceutical design · 2024Article
- High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity againstJournal of fungi (Basel, Switzerland) · 2023Article
- Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring.Frontiers in pharmacology · 2023Review
- Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology.Pharmaceutics · 2021Article
- Population Pharmacokinetics and Initial Dose Optimization of Sirolimus Improving Drug Blood Level for Seizure Control in Pediatric Patients With Tuberous Sclerosis Complex.Frontiers in pharmacology · 2021Article
- Optimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma.Frontiers in pharmacology · 2021Article
- Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real-world data.Experimental and therapeutic medicine · 2020Article
- Review
- Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex.Frontiers in pharmacology · 2020Article
- Population pharmacokinetics of sirolimus in pediatric patients with kaposiform hemangioendothelioma: A retrospective study.Oncology letters · 2019Article
- Population pharmacokinetics of temsirolimus and sirolimus in children with recurrent solid tumours: a report from the Children's Oncology Group.British journal of clinical pharmacology · 2017Article
- The first study in pediatric: Population pharmacokinetics of sirolimus and its application in Chinese children with immune cytopenia.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
aimsTemsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR). Pharmacokinetic (PK) characterization of temsirolimus in children is limited and there is no paediatric temsirolimus population PK model available. The objective of this study was to simultaneously characterize the PK of temsirolimus and its metabolite sirolimus in paediatric patients with recurrent solid or central nervous system tumours and to develop a population PK model.
methodsThe PK data for temsirolimus and sirolimus were collected as a part of a Children's Oncology Group phase I clinical trial in paediatric patients with recurrent solid tumours. Serial blood concentrations obtained from 19 patients participating in the PK portion of the study were used for the analysis. Population PK analysis was performed by nonlinear mixed effect modelling using NONMEM.
resultsA three-compartment model with zero-order infusion was found to best describe temsirolimus PK. Allometrically scaled body weight was included in the model to account for body size differences. Temsirolimus dose was identified as a significant covariate on clearance. A sirolimus metabolite formation model was developed and integrated with the temsirolimus model. A two-compartment structure model adequately described the sirolimus data.
conclusionThis study is the first to describe a population PK model of temsirolimus combined with sirolimus formation and disposition in paediatric patients. The developed model will facilitate PK model-based dose individualization of temsirolimus and the design of future clinical studies in children.
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