ArticleCPT: pharmacometrics & systems pharmacology2018
Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules.
Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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
10 citing papers in PubMed.
- Intestinal Organoid-Based Mathematical Modeling Predicts Clinical Gastrointestinal Toxicity of Oral Oncology Drugs.CPT: pharmacometrics & systems pharmacology · 2026Article
- A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity.CPT: pharmacometrics & systems pharmacology · 2023Article
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Application of the Nested Enzyme-Within-Enterocyte (NEWE) Turnover Model for Predicting the Time Course of Pharmacodynamic Effects.CPT: pharmacometrics & systems pharmacology · 2020Article
- Safety Considerations of Cancer Nanomedicine-A Key Step toward Translation.Small (Weinheim an der Bergstrasse, Germany) · 2020Review
- A Citrulline-Based Translational Population System Toxicology Model for Gastrointestinal-Related Adverse Events Associated With Anticancer Treatments.CPT: pharmacometrics & systems pharmacology · 2019Article
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- Reproducibility of Quantitative Systems Pharmacology Models: Current Challenges and Future Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Review
- Human 3D Gastrointestinal Microtissue Barrier Function As a Predictor of Drug-Induced Diarrhea.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Quantitative translational modeling to facilitate preclinical to clinical efficacy & toxicity translation in oncology.Future science OA · 2018Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastrointestinal (GI) adverse events (AEs) are frequently dose limiting for oncology agents, requiring extensive clinical testing of alternative schedules to identify optimal dosing regimens. Here, we develop a translational mathematical model to predict these clinical AEs starting from preclinical GI toxicity data. The model structure incorporates known biology and includes stem cells, daughter cells, and enterocytes. Published data, including cellular numbers and division times, informed the system parameters for humans and rats. The drug-specific parameters were informed with preclinical histopathology data from rats treated with irinotecan. The model fit the rodent irinotecan-induced pathology changes well. The predicted time course of enterocyte loss in patients treated with weekly doses matched observed AE profiles. The model also correctly predicts a lower level of AEs for every 3 weeks (Q3W), as compared to the weekly schedule.
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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.