ArticleFrontiers in pharmacology2012
A multi-scale modeling framework for individualized, spatiotemporal prediction of drug effects and toxicological risk.
Article in Frontiers in pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Application of Magnetic Resonance Imaging in Liver Biomechanics: A Systematic Review.Frontiers in physiology · 2021Pooled it
- A systems pharmacology model for paracetamol overdose and treatment.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- From Knowledge Graphs to Digital Twins: Perspectives on Modeling Patient Outcomes for Health Care Quality Assessment.Journal of medical Internet research · 2026Article
- Multiscale modeling of drug-induced liver injury from organ to lobule.NPJ digital medicine · 2025Article
- A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction.NPJ digital medicine · 2024Article
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Article
- Analgesic Action of Acetaminophen via Kv7 Channels.International journal of molecular sciences · 2022Article
- Unraveling the effect of intra- and intercellular processes on acetaminophen-induced liver injury.NPJ systems biology and applications · 2022Article
- Multiscale Model of Antiviral Timing, Potency, and Heterogeneity Effects on an Epithelial Tissue Patch Infected by SARS-CoV-2.Viruses · 2022Article
- From Seeing to Simulating: A Survey of Imaging Techniques and Spatially-Resolved Data for Developing Multiscale Computational Models of Liver Regeneration.Frontiers in systems biology · 2022Article
- Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.Frontiers in physiology · 2021Review
- Virtual Lobule Models Are the Key for Multiscale Biomechanical and Pharmacological Modeling for the Liver.Frontiers in physiology · 2020Article
- Systems Toxicology Approach to Identifying Paracetamol Overdose.CPT: pharmacometrics & systems pharmacology · 2018Article
- Article
- Bridging the Data Gap FromFrontiers in public health · 2018Review
- The virtual cell based assay: Current status and future perspectives.Toxicology in vitro : an international journal published in association with BIBRA · 2017Article
- Article
- Computational Modeling in Liver Surgery.Frontiers in physiology · 2017Review
- The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions.Environmental health perspectives · 2016Review
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 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we focus on a novel multi-scale modeling approach for spatiotemporal prediction of the distribution of substances and resulting hepatotoxicity by combining cellular models, a 2D liver model, and whole body model. As a case study, we focused on predicting human hepatotoxicity upon treatment with acetaminophen based on in vitro toxicity data and potential inter-individual variability in gene expression and enzyme activities. By aggregating mechanistic, genome-based in silico cells to a novel 2D liver model and eventually to a whole body model, we predicted pharmacokinetic properties, metabolism, and the onset of hepatotoxicity in an in silico patient. Depending on the concentration of acetaminophen in the liver and the accumulation of toxic metabolites, cell integrity in the liver as a function of space and time as well as changes in the elimination rate of substances were estimated. We show that the variations in elimination rates also influence the distribution of acetaminophen and its metabolites in the whole body. Our results are in agreement with experimental results. What is more, the integrated model also predicted variations in drug toxicity depending on alterations of metabolic enzyme activities. Variations in enzyme activity, in turn, reflect genetic characteristics or diseases of individuals. In conclusion, this framework presents an important basis for efficiently integrating inter-individual variability data into models, paving the way for personalized or stratified predictions of drug toxicity and efficacy.
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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.