ArticleArchives of toxicology2020
Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone.
Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Cross-species comparisons of plasma binding and considerations for data evaluation.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
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- A novel method to derive a human safety limit for PFOA by gene expression profiling and modelling.Frontiers in toxicology · 2024Article
- Application of high throughput in vitro metabolomics for hepatotoxicity mode of action characterization and mechanistic-anchored point of departure derivation: a case study with nitrofurantoin.Archives of toxicology · 2023Article
- New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians.Environmental toxicology and chemistry · 2023Review
- Review
- In vitro-in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans.Archives of toxicology · 2022Article
- Inter-individual variation in chlorpyrifos toxicokinetics characterized by physiologically based kinetic (PBK) and Monte Carlo simulation comparing human liver microsome and SupersomeArchives of toxicology · 2022Article
- Use of Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict In Vivo Acute Toxicity of Tetrodotoxin in Rodents.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of tobacco and other nicotine-containing products.Frontiers in toxicology · 2022Article
- Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon.Archives of toxicology · 2021Article
- Derivation of a Human In Vivo Benchmark Dose for Bisphenol A from ToxCast In Vitro Concentration Response Data Using a Computational Workflow for Probabilistic QuantitativeFrontiers in pharmacology · 2021Article
- Derivation of a Human In Vivo Benchmark Dose for Perfluorooctanoic Acid From ToxCast In Vitro Concentration-Response Data Using a Computational Workflow for Probabilistic Quantitative In Vitro to In Vivo Extrapolation.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration-response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose-response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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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.