ArticlePharmaceutical research2008
Modeling and simulation of hepatic drug disposition using a physiologically based, multi-agent in silico liver.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.PLoS computational biology · 2020Article
- Liver Bioreactor Design Issues of Fluid Flow and Zonation, Fibrosis, and Mechanics: A Computational Perspective.Journal of functional biomaterials · 2020Review
- Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Article
- In silico drug absorption tract: An agent-based biomimetic model for human oral drug absorption.PloS one · 2018Article
- Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.PLoS computational biology · 2016Article
- A physiologically-based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models.Theoretical biology & medical modelling · 2016Article
- Virtual Experiments Enable Exploring and Challenging Explanatory Mechanisms of Immune-Mediated P450 Down-Regulation.PloS one · 2016Article
- Article
- Toward modular biological models: defining analog modules based on referent physiological mechanisms.BMC systems biology · 2014Article
- Heat Shock Protein 70 Expression is Increased in the Liver of Neonatal Intrauterine Growth Retardation Piglets.Asian-Australasian journal of animal sciences · 2012Article
- Cloud computing and validation of expandable in silico livers.BMC systems biology · 2010Article
- Drug structure-transport relationships.Journal of pharmacokinetics and pharmacodynamics · 2010Review
- Computational experiments reveal plausible mechanisms for changing patterns of hepatic zonation of xenobiotic clearance and hepatotoxicity.Journal of theoretical biology · 2010Article
- At the biological modeling and simulation frontier.Pharmaceutical research · 2009Review
- Tissue-level modeling of xenobiotic metabolism in liver: An emerging tool for enabling clinical translational research.Clinical and translational science · 2009Article
- Essential operating principles for tumor spheroid growth.BMC systems biology · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeValidate a physiologically based, mechanistic, in silico liver (ISL) for studying the hepatic disposition and metabolism of antipyrine, atenolol, labetalol, diltiazem, and sucrose administered alone or in combination. MATERIALS AND
methodsAutonomous software objects representing hepatic components such as metabolic enzymes, cells, and microarchitectural details were plugged together to form a functioning liver analogue. Microarchitecture features were represented separately from drug metabolizing functions. Each ISL component interacts uniquely with mobile objects. Outflow profiles were recorded and compared to wet-lab data. A single ISL structure was selected, parameterized, and held constant for all compounds. Parameters sensitive to drug-specific physicochemical properties were tuned so that ISL outflow profiles matched in situ outflow profiles.
resultsISL simulations were validated separately and together against in situ data and prior physiologically based pharmacokinetic (PBPK) predictions. The consequences of ISL parameter changes on outflow profiles were explored. Selected changes altered outflow profiles in ways consistent with knowledge of hepatic anatomy and physiology and drug physicochemical properties.
conclusionsA synthetic, agent-oriented in silico liver has been developed and successfully validated, enabling us to posit that static and dynamic ISL mechanistic details, although abstract, map realistically to hepatic mechanistic details in PBPK simulations.
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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.