MPS and In Silico Modeling: The next generation of bioavailability prediction

Oral bioavailability is a critical pharmacokinetic parameter that must be determined when evaluating new drug candidates. Accurate estimations are essential for establishing safe dosing for first-in-human trials and determining effective therapeutic regimens.

Traditional preclinical approaches, such as 2D in vitro cell cultures and in vivo animal studies, are constrained by physiological and human relevance, which can limit the accuracy of bioavailability predictions. To address these in vitro to in vivo extrapolation (IVIVE) challenges, fluidically linked multi-organ human-relevant microphysiological systems (MPS) can be used to better simulate human physiology.

In this webinar, we showcase how combining the PhysioMimix® Gut/Liver-on-a-chip and in silico modeling enables prediction of ADME parameters and oral bioavailability for the CYP3A4-metabolized compound – midazolam.

We will also show how MPS and in silico modeling enhances our ability to derive both gut- and liver-specific ADME parameters. Finally, we guide you through our unique methodology for developing the mechanistic models and estimating ADME parameters, offering insights into how MPS platforms can be used to bridge the gap between in vitro and in vivo data.

Key Learning Objectives

• Understand how MPS data is integrated with in silico modeling to predict key gut- and liver-specific ADME parameters
• Explore the advantages of using primary human gut and liver MPS models, especially for compounds metabolized in the gut.
• Learn our unique approach to predicting oral bioavailability (F) by first estimating Fa, Fg, and Fh.
• Discover how a single gut/liver experiment can yield up to 10 ADME parameters

Note that from October 2025, PhysioMimix® OOC Single-organ, Multi-organ, and Higher throughput (HT) Systems that may be mentioned in the broadcast have now been replaced by one universal PhysioMimix Core microphysiological system.

Speakers

Morné van Wyk

Senior Computational Scientist

As a Senior Computational Scientist, Morné is involved in building mathematical models and tools to analyse Organ-on-chip experiments. Morné completed his PhD in biochemistry at the University of Stellenbosch, South Africa, where he focused on computational cell biology and systems biology.

Marco Ortiz

Senior Scientist, CN Bio

Dr. Marco Ortiz has experience in developing cell types as commercial products and clinical therapeutics. In his most recent role, he performed preclinical experiments on iPSC-derived hepatocytes for acute liver diseases as a potential indication. Marco Ortiz completed a bachelor’s in genomic sciences working at the University of Wisconsin-Madison and completed a UCL Wellcome Trust PhD programme at the Francis Crick Institute.