ArticleFrontiers in pharmacology2023
Integrating distribution kinetics and toxicodynamics to assess repeat dose neurotoxicity
Article in Frontiers in pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Neuronal safety of Kv11.1 blockers: Patch-clamp and in vitro evaluation with physiologically based pharmacokinetic (PBPK) modeling.Toxicology reports · 2026Article
- Extrapolation steps in quantitativeCurrent research in toxicology · 2026Review
- In Silico Forensic Toxicology: Is It Feasible?Toxics · 2025Review
- Novel Strategy to Assess the Neurotoxicity of Organic Solvents Such as Glycol Ethers: Protocol for Combining In Vitro and In Silico Methods With Human-Controlled Exposure Experiments.JMIR research protocols · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription-polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental
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