Gut–Liver Microphysiological System for Oral Bioavailability Prediction
Poster Authors:
Lijun Gao, Jing Lai, Hong Zhang, Yang You, Chunyan Han, Mandy Xu
1in vitro ADMET, Pharmaron Beijing Co., Ltd. (China)
Poster: hiSIEC-Based Gut–Liver MPS for Predicting Human Oral Bioavailability
Human oral bioavailability is driven by a mix of intestinal absorption, gut metabolism, and hepatic first-pass extraction. We present a novel gut–liver microphysiological system (MPS) that combines iPSC-derived intestinal cells with primary human hepatocytes to better replicate human physiology in vitro.
Advanced Human Oral Bioavailability Assessment
Integrated gut–liver models are capable of capturing intestinal absorption, gut metabolism, and liver first-pass effects in a single system. With improved physiological relevance, hiSIEC cells demonstrate functional enzyme and transporter activity (CYP3A4, P-gp, BCRP, PEPT1), enabling better IVIVC vs traditional models. This model demonstrates superior in vitro–in vivo correlation compared to Caco-2 systems, stable co-culture performance and ensures both intestinal and hepatic components maintain functionality during experiments.
The problem with estimating oral bioavailability is that static models of one system (such as Caco-2) cannot recapitulate the effects of intestinal permeability, metabolism, and hepatic clearance collectively, leading to inaccuracies in estimating human oral exposure.
This poster introduces a next-generation gut–liver MPS approach by using a dual-organ MPS platform integrating:
Capabilities
- hiSIEC intestinal monolayers with strong barrier integrity (TEER 300–400 Ω·cm²)
- Primary human hepatocytes to simulate liver metabolism
- Active enzyme and transporter systems reflecting human biology
In this poster, we demonstrate how the system enables dynamic modelling of absorption–metabolism interactions, improving translational relevance.
The model successfully captured absorption, metabolism, and first-pass extraction using midazolam as a model compound. In addition, it demonstrated distinct behaviour vs Caco-2 models, showing system sensitivity to complex ADME processes. It showed enhanced prediction of human oral bioavailability (F) through the integrated modelling approach.
Takeaway
The hiSIEC-based gut–liver MPS provides a more predictive and physiologically relevant platform for oral drug development when compared to more standard single-system models. This enables researchers to make better decisions earlier in the development process.
Why Pharmaron?
Pharmaron offers advanced in vitro ADME and MPS solutions, including:
- Integrated multi-organ platforms
- Expertise in IVIVE and oral bioavailability prediction
- Global DMPK capabilities across discovery and development
