Drug Metabolism
Standard in vitro DMPK studies face many challenges including, incompatibility with new therapeutic modalities, inaccurate predictions of human in vivo clearance rates (particularly for low clearance compounds) and missing rare or human-specific metabolites
PhysioMimix™ Organ-on-a-Chip gives unique insights into rates of metabolism and the role of metabolites.
Drug Metabolism Studies using PhysioMimix™ OOC
PhysioMimix™ Organ-on-a-Chip Systems can be used to study human drug absorption, distribution, metabolism and excretion (ADME) to help inform parameters such as dosage regime and effective drug concentration. To date, these insights have been gained using single-organ tissue models, often built from multiple cell types, however, the new PhysioMimix Multi-Organ offers a unique capability to improve the prediction of in vivo pharmacokinetics and pharmacodynamics by interconnecting two tissues related to ADME.
For example, combining the liver with a gut model, orally administered drugs can be studied in a single system that accounts for compound permeability through an intestinal barrier, hepatic metabolism, organ-organ interaction and crosstalk.
PhysioMimix™ OOC enables users to:
3D Liver tissues, generated on CN Bio’s PhysioMimix OOC platform, recreate the liver microarchitecture and maintain its phenotype for more than four weeks.
- Model a human environment, generate human-specific metabolites and overcome cross-species issues
- Culture metabolically active cells for longer term studies, ensuring compounds are metabolised and all relevant metabolites are observed
- Repeatedly sample from the same well to profile concentration changes over time and determine translationally relevant PK parameters for improved in vitro to in vivo translation
The liver is the principal site of drug metabolism. CN Bio’s Liver-on-a-chip system is ideal for hepatic clearance, including low clearance compounds and metabolic profiles studies. Our Gut-on-a-chip system enables researchers to investigate apparent drug permeability and intestinal metabolism. When combined, our Gut-Liver multi-organ model provides the human in vitro alternative to animal or in silico first pass metabolism studies (ADME).
Need fast-track human-relevant information regarding lead candidate drug metabolism?
Submit your lead candidates for test using our Drug Metabolism Testing Services
Detecting compounds with varying clearance rates – clearance of disopyramide (yellow) , diclofenac (pink) and phenacetin (green) in LC12 plates
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Predicting human hepatic clearance – comparison of in vivo and liver-on-chip hepatic clearance rates of five common molecules
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In vitro In vivo extrapolation – population-based PK model of Lidocaine clearance
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Related resources
WEBINAR
Testing on Humans: How to Predict Hepatotoxicity and Drug Clearance Ahead of Clinical Trials Using Liver-on-a-Chip
SCIENTIFIC PAPER
Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System
Collaborating With Regulators
In 2018 CN Bio signed a multi-year deal with the US Food and Drug Administration (FDA), the world’s most prominent pharmaceutical regulatory agency. The first aim of this collaboration was to evaluate the use of CN Bio’s PhysioMimix Liver-on-a-chip for drug interaction and safety studies.
In 2021, the FDA published the results of their study findings with CN Bio. This co-publication:
- represents the first co-published, peer-reviewed article between a microphysiological system provider and a regulator
- demonstrates advantages of PhysioMimix™ in drug safety and metabolism applications
WEBINAR
A Regulators Viewpoint: Establishing Strategies To Evaluate Microphysiological Systems for Drug Development. Join Dr Alexandre Ribeiro, Staff Fellow (Biological Scientist) at the FDA.
SCIENTIFIC PAPER
Characterizing the Reproducibility in Using a Liver Microphysiological System for Assaying Drug Toxicity, Metabolism and Accumulation
Human organ
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Translatable
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