ArticleScientific reports2023
Development of rat duodenal monolayer model with effective barrier function from rat organoids for ADME assay.
Article in Scientific reports, 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, 6 citations in OpenAlex.
- Engineered Decellularized Matrix Hydrogels with Crypt-Villus Topography for Forming Functional Intestinal Epithelium.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Robust and reproducible human intestinal organoid-derived monolayer model for analyzing drug absorption.Scientific reports · 2025Article
- Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.Molecular pharmaceutics · 2024Review
- New Generation of Orthodontic Elastomeric Ligature to Prevent Enamel Demineralization In Vivo.International journal of molecular sciences · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The in-depth analysis of the ADME profiles of drug candidates using in vitro models is essential for drug development since a drug's exposure in humans depends on its ADME properties. In contrast to efforts in developing human in vitro absorption models, only a limited number of studies have explored models using rats, the most frequently used species in in vivo DMPK studies. In this study, we developed a monolayer model with an effective barrier function for ADME assays using rat duodenal organoids as a cell source. At first, we developed rat duodenal organoids according to a previous report, but they were not able to generate a confluent monolayer. Therefore, we modified organoid culture protocols and developed cyst-enriched organoids; these strongly promoted the formation of a confluent monolayer. Furthermore, adding valproic acid to the culture accelerated the differentiation of the monolayer, which possessed an effective barrier function and apicobasal cell polarity. Drug transporter P-gp function as well as CYP3A activity and nuclear receptor function were confirmed in the model. We expect our novel monolayer model to be a useful tool for elucidating drug absorption processes in detail, enabling the development of highly absorbable drugs.
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