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, often lack physiological complexity or human relevance required for accurate bioavailability predictions. To address the limitations of in vitro to in vivo extrapolation (IVIVE), we can leverage a multi-organ human-relevant microphysiological systems (MPS) that use fluidically linked, multi-organ models 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

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 of iPSCs derived hepatocytes for acute liver diseases as a potential indication. Marco Ortiz completed a bachelors in genomic sciences working at the University of Wisconsin-Madison and completed a UCL Wellcome Trust PhD programme at the Francis Crick Institute.