ArticlePharmaceutical research2018
A Multiscale Physiologically-Based Pharmacokinetic Model for Doxorubicin to Explore its Mechanisms of Cytotoxicity and Cardiotoxicity in Human Physiological Contexts.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 45 citations in OpenAlex.
- Bellidifolin alleviates doxorubicin-induced hepatotoxicity: a study integrating network pharmacology, molecular docking, and experimental validation.Die Naturwissenschaften · 2026Article
- Evaluating Seeding Density Effects on Cardiac Organoid Health and Functionality for Toxicity Studies.Tissue engineering. Part A · 2026Article
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Janus Nanoparticles in Doxorubicin Delivery: A New Frontier in Targeted Cancer Treatment.Materials (Basel, Switzerland) · 2026Review
- Opportunities for machine learning and artificial intelligence in physiologically-based pharmacokinetic (PBPK) modeling.Advanced drug delivery reviews · 2025Review
- Aegeline improves doxorubicin-induced liver toxicity by modulating oxidative stress and Bax/Bcl2/caspase/NF-κB signaling.Scientific reports · 2025Article
- An In Silico Platform to Predict Cardiotoxicity Risk of Anti-tumor Drug Combination with hiPSC-CMs Based In Vitro Study.Pharmaceutical research · 2024Article
- Translational Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Oxaliplatin and Irinotecan in Colorectal Cancer.Pharmaceutics · 2023Article
- Review
- Susceptibility to adriamycin-induced hepatotoxicity in mice depends on PRKDC polymorphism.The Journal of veterinary medical science · 2023Article
- Functionalized liposomes for targeted breast cancer drug delivery.Bioactive materials · 2023Review
- In vitro to clinical translational pharmacokinetic/pharmacodynamic modeling of doxorubicin (DOX) and dexrazoxane (DEX) interactions: Safety assessment and optimization.Scientific reports · 2023Article
- Predictive Design and Analysis of Drug Transport by Multiscale Computational Models Under Uncertainty.Pharmaceutical research · 2023Review
- Article
- Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances.Drug delivery and translational research · 2022Article
- Overexpression of Programmed Cell Death 1 Prevents Doxorubicin-Induced Apoptosis Through Autophagy Induction in H9c2 Cardiomyocytes.Cardiovascular toxicology · 2022Article
- Physiologically Based Pharmacokinetic Modelling and Simulation to Predict the Plasma Concentration Profile of Doxorubicin.Pharmaceutics · 2022Article
- Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy.Frontiers in pharmacology · 2022Review
- A quantitative systems pharmacology approach to predict the safe-equivalent dose of doxorubicin in patients with cardiovascular comorbidity.CPT: pharmacometrics & systems pharmacology · 2021Article
- Apply a Physiologically Based Pharmacokinetic Model to Promote the Development of Enrofloxacin Granules: Predict Withdrawal Interval and Toxicity Dose.Antibiotics (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThe mechanisms underlying doxorubicin cytotoxicity and cardiotoxicity were broadly explored but remain incompletely understood. A multiscale physiologically-based pharmacokinetic (PBPK) model was developed to assess doxorubicin dispositions at levels of system, tissue interstitial, cell, and cellular organelles. This model was adopted to explore the mechanisms-of-action/toxicity of doxorubicin in humans.
methodsThe PBPK model was developed by analyzing data from mice and the model was verified by scaling up to predict doxorubicin multiscale dispositions in rats and humans. The multiscale dispositions of doxorubicin in human heart and tumors were explicitly simulated to elucidate the potential mechanisms of its cytotoxicity and cardiotoxicity.
resultsThe developed PBPK model was able to adequately describe doxorubicin dispositions in mice, rats and humans. In humans, prolonged infusion, a dosing regimen with less cardiotoxicity, was predicted with substantially reduced free doxorubicin concentrations at human heart interstitium, which were lower than the concentrations associated with oxidative stress. However, prolonged infusion did not reduce doxorubicin-DNA adduct at tumor nucleus, consistent with clinical observations that prolonged infusion did not compromise anti-tumor effect, indicating that one primary anti-tumor mechanism was DNA torsion.
conclusionsA multiscale PBPK model for doxorubicin was developed and further applied to explore its cytotoxic and cardiotoxic mechanisms.
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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.