ArticlePloS one2014
Dose schedule optimization and the pharmacokinetic driver of neutropenia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Multiscale and Translational Quantitative Systems Toxicology, Pharmacokinetic-Toxicodynamic Modeling Analysis for Assessment of Doxorubicin-Induced Cardiotoxicity.The AAPS journal · 2021Article
- Pharmacokinetics and Toxicities of Oral Docetaxel Formulations Co-Administered with Ritonavir in Phase I Trials.Clinical pharmacology : advances and applications · 2021Article
- Optimization of clinical dosing schedule to manage neutropenia: learnings from semi-mechanistic modeling simulation approach.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Chemotherapy-Induced Neutropenia as a Prognostic and Predictive Marker of Outcomes in Solid-Tumor Patients.Drugs · 2018Review
- Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules.CPT: pharmacometrics & systems pharmacology · 2018Article
- Frequency-Domain Response Analysis for Quantitative Systems Pharmacology Models.CPT: pharmacometrics & systems pharmacology · 2017Article
- Translational Modeling of Drug-Induced Myelosuppression and Effect of Pretreatment Myelosuppression for AZD5153, a Selective BRD4 Inhibitor.CPT: pharmacometrics & systems pharmacology · 2017Article
- Modeling and Simulation Approaches for Cardiovascular Function and Their Role in Safety Assessment.CPT: pharmacometrics & systems pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxicity often limits the utility of oncology drugs, and optimization of dose schedule represents one option for mitigation of this toxicity. Here we explore the schedule-dependency of neutropenia, a common dose-limiting toxicity. To this end, we analyze previously published mathematical models of neutropenia to identify a pharmacokinetic (PK) predictor of the neutrophil nadir, and confirm this PK predictor in an in vivo experimental system. Specifically, we find total AUC and Cmax are poor predictors of the neutrophil nadir, while a PK measure based on the moving average of the drug concentration correlates highly with neutropenia. Further, we confirm this PK parameter for its ability to predict neutropenia in vivo following treatment with different doses and schedules. This work represents an attempt at mechanistically deriving a fundamental understanding of the underlying pharmacokinetic drivers of neutropenia, and provides insights that can be leveraged in a translational setting during schedule selection.
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Registered trials
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.