ArticleBritish journal of clinical pharmacology2018
Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer.Cancer chemotherapy and pharmacology · 2021Trial
- A large multicentre, randomized, double-blind, cross-over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US- and EU-reference biologics.British journal of clinical pharmacology · 2020Trial
- A sustained-release depot formulation of β-nicotinamide mononucleotide for alleviating chemotherapy-induced myelosuppression.Materials today. Bio · 2026Article
- Prediction of neutrophil nadir and recovery following paediatric haematopoietic cell transplantation with busulfan conditioning.British journal of clinical pharmacology · 2026Article
- Continuous multidimensional physiological monitoring redefines early warning and preemptive treatment for neutropenic sepsis following cisplatin chemotherapy in non-small cell lung cancer.Frontiers in pharmacology · 2026Article
- FDA-AACR Strategies for Optimizing Dosages for Oncology Drug Products: Selecting Optimized Dosages for Registrational Trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Population Pharmacokinetic-Pharmacodynamic Modeling of Granulocyte Colony-Stimulating Factor to Optimize Dosing and Timing for CD34Clinical and translational science · 2025Article
- Clinical decision support for chemotherapy-induced neutropenia using a hybrid pharmacodynamic/machine learning model.CPT: pharmacometrics & systems pharmacology · 2023Article
- Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy.CPT: pharmacometrics & systems pharmacology · 2023Article
- Navigating Between Right, Wrong, and Relevant: The Use of Mathematical Modeling in Preclinical Decision Making.Frontiers in pharmacology · 2022Article
- Impact of granulocyte colony-stimulating factor on FOLFIRINOX-induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach.British journal of clinical pharmacology · 2020Article
- Prediction of Survival Benefit of Filgrastim in Adult and Pediatric Patients With Acute Radiation Syndrome.Clinical and translational science · 2020Article
- Quantification of Radiation Injury on Neutropenia and the Link between Absolute Neutrophil Count Time Course and Overall Survival in Nonhuman Primates Treated with G-CSF.Pharmaceutical research · 2020Article
- Drug Exposure to Establish Pharmacokinetic-Response Relationships in Oncology.Clinical pharmacokinetics · 2020Review
- IL-6 -572C>G and CARD8 304T>A Genetic Polymorphisms are Associated with the Absolute Neutrophil Count in Patients with Hematological Malignancies Under Chemotherapy: An Application of Multilevel Models to a Preliminary Pharmacogenetic Study.Pharmacogenomics and personalized medicine · 2020Article
- Pharmacokinetic-Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High-Dose Melphalan for Autologous Stem Cell Transplant.CPT: pharmacometrics & systems pharmacology · 2018Article
- Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.British journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe objective of the present study was to use pharmacokinetic-pharmacodynamic modelling to characterize the effects of chemotherapy on the granulopoietic system and to predict the absolute neutrophil counts (ANCs) for patients with chemotherapy-induced neutropenia treated with filgrastim and pegfilgrastim.
methodsData were extracted from 10 phase I-III studies conducted in 110 healthy adults, and 618 adult and 52 paediatric patients on chemotherapy following administration of filgrastim or pegfilgrastim. The structural model accounted for ANC dynamics and the effects of filgrastim and pegfilgrastim, chemotherapy and corticosteroids. The impact of neutrophils on drug disposition was based on a drug receptor-binding model that assumed quasi-equilibrium and stimulation of the production and maturation of neutrophils upon treatment. The chemotherapy and corticosteroid effects were represented by kinetic-pharmacodynamic-type models, where chemotherapy stimulated elimination of neutrophil precursors at the mitotic stage, and corticosteroids stimulated neutrophil production.
resultsThe systemic half-lives of filgrastim (2.6 h) and pegfilgrastim (10.1 h) were as expected. The effective half-life of chemotherapy was 9.6 h, with a 2-day killing effect. The rate of receptor elimination from mitotic compartments exhibited extreme interindividual variability (% coefficient of variation >200), suggesting marked differences in sensitivity to chemotherapy effects on ANCs. The stimulatory effects of pegfilgrastim were significantly greater than those of filgrastim. Model qualification confirmed the predictive capability of this model.
conclusionThis qualified model simulates the time course of ANC in the absence or presence of chemotherapy and predicts nadir, time to nadir and time of recovery from different grades of neutropenia upon treatment with filgrastim and pegfilgrastim.
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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.