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Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality

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Establishing the Human Duodenum Chip as a Surrogate for Effective Human Permeability: In Vitro and In Silico

Kellyn M Patros Zagaja¹, Anna K Kopec¹, Julie Harney¹

¹Pfizer Research and Development, Pfizer Inc., Groton, Connecticut, 06340, USA.

The AAPS Journal

|October 31, 2025

Summary

Organoids-on-a-chip offer a human-specific platform for drug permeability assessment, improving predictions of oral bioavailability and reducing reliance on animal models.

Keywords:

PBPK modeling biopharmaceutics oral absorption organ-on-a-chip organoids permeability

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Canine Intestinal Organoids in a Dual-Chamber Permeable Support System

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Published on: March 2, 2022

Area of Science:

Biotechnology
Pharmacology
Drug Discovery

Background:

Drug permeability across epithelial barriers is crucial for oral drug efficacy.
Traditional models like animals and cell cultures lack human intestinal complexity.
Organoids and organ-on-a-chip technologies provide physiologically relevant, human-specific platforms.

Purpose of the Study:

To evaluate drug permeability using human intestinal organoids-on-a-chip.
To benchmark this technology against conventional cell lines.
To predict systemic drug exposure using simulation software.

Main Methods:

Utilized the Emulate human duodenum-on-a-chip platform with three model compounds (lisinopril, metoprolol, fluconazole).
Measured apparent permeability (P_app) and correlated it with literature-reported effective permeability (P_eff).
Implemented linear regression in Simcyp® Simulator and GastroPlus™ to predict systemic exposure.

Main Results:

Organoid-on-a-chip models demonstrated physiologically relevant drug transport measurements.
Linear regression successfully correlated P_app with P_eff for model compounds.
Predicted systemic exposure aligned with observed plasma concentration-time profiles.

Conclusions:

Human organoids-on-a-chip are a valuable tool for accurate drug permeability assessment.
This technology enhances the prediction of oral bioavailability and reduces ethical concerns associated with animal testing.
The integration with simulation software improves in silico prediction of drug pharmacokinetics.