ArticleThe Journal of pharmacology and experimental therapeutics2013
Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 58 citations in OpenAlex.
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Clemizole inhibits CrtN-driven staphyloxanthin biosynthesis in Staphylococcus aureus to enhance host immune clearance.Communications biology · 2026Article
- Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism.Toxicological research · 2025Review
- Investigation of Biotransformation Pathways in a Chimeric Mouse with a Humanized Liver.International journal of molecular sciences · 2025Article
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Contribution of Humanized Liver Chimeric Mice to the Study of Human Hepatic Drug Transporters: State of the Art and Perspectives.European journal of drug metabolism and pharmacokinetics · 2022Review
- Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.Stem cell research & therapy · 2021Review
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Antiretroviral Drug Metabolism in Humanized PXR-CAR-CYP3A-NOG Mice.The Journal of pharmacology and experimental therapeutics · 2018Article
- Observation of Clinically Relevant Drug Interaction in Chimeric Mice with Humanized Livers: The Case of Valproic Acid and Carbapenem Antibiotics.European journal of drug metabolism and pharmacokinetics · 2017Article
- Human hepatic organoids for the analysis of human genetic diseases.JCI insight · 2017Article
- A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism.Nature communications · 2017Article
- Long-term culture of human liver tissue with advanced hepatic functions.JCI insight · 2017Article
- Screening of conventional anticonvulsants in a genetic mouse model of epilepsy.Annals of clinical and translational neurology · 2017Article
- Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.Brain : a journal of neurology · 2017Article
- Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection.Virology · 2017Article
- Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells.British journal of pharmacology · 2017Article
- Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools.Current drug metabolism · 2017Review
- Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells.Journal of visualized experiments : JoVE · 2016Article
Corrections and comments
- Erratum issuedNishimura, Toshiko [corrected to Nishimura, Toshihiko]
Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data to predict the drug metabolites or potential drug-drug interactions (DDIs) that will occur in humans. Although chimeric mice with humanized livers can produce known human metabolites for test substrates, we do not know whether chimeric mice can be used to prospectively predict human drug metabolism or a possible DDI. Therefore, we investigated whether they could provide a more predictive assessment for clemizole, a drug in clinical development for the treatment of hepatitis C virus (HCV) infection. Our results demonstrate, for the first time, that analyses performed in chimeric mice can correctly identify the predominant human drug metabolite before human testing. The differences in the rodent and human pathways for clemizole metabolism were of importance, because the predominant human metabolite was found to have synergistic anti-HCV activity. Moreover, studies in chimeric mice also correctly predicted that a DDI would occur in humans when clemizole was coadministered with a CYP3A4 inhibitor. These results demonstrate that using chimeric mice can improve the quality of preclinical drug assessment.
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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.