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The Power of 3D Liver Culture Models for More Predictive and Insightful DMPK Studies

Published: Tuesday, December 03, 2013
Last Updated: Tuesday, December 03, 2013
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LiverChip™ enables robust and reproducible prediction of metabolic clearance in humans and provides extended time course for the study of low clearance compounds.

Zyoxel announces preliminary results from a testing by Sanofi on Zyoxel’s LiverChip™ platform for drug metabolism and pharmacokinetic (DMPK) studies. Sanofi employed a variety of morphological, genetic and functional analyses to fully characterise the LiverChip™ system, the full findings of which will be presented as part of Zyoxel’s In Vitro Liver Technology Symposium taking place on December 10, 2013 in Oxford, UK.

Under the terms of an Equipment Hire Agreement, Sanofi, an integrated global healthcare leader, has been exploring the utility of Zyoxel’s LiverChip™ platform. During the project, which commenced in December 2012 and involved the installation of a LiverChip™ device at a Sanofi research site, the company tested the human hepatocyte LiverChip™ system against current industry gold standard 2D plated cultures of primary hepatocytes. 

Using LiverChip™, Sanofi’s researchers were able to perform in depth DMPK analyses over much longer time courses of up to 6 days, including the accurate monitoring of dose clearance by the cytochrome P450 enzyme superfamily (CYPs), as well as the induction of CYP isoforms during drug metabolism. The study also confirmed that LiverChip™ does not suffer from any non-specific drug binding, while the results exhibited good reproducibility, both within individual plates and between replicate experiments. 

Extending the duration of cell culture increases pharmaceutical value and relevance 
As Dr. Emma Sceats, Chief Operating Officer of Zyoxel, summarised: “Sanofi have been a very good partner and customer of Zyoxel, and are one of an increasing number of international pharmaceutical companies we are working with. The value proposition of LiverChip’s™ extended time window is proving especially useful for applications such as assessing low clearance compounds, formation and detection of rare metabolites and to study the impact of chronic multiple dosing. We believe that the system can become part of the routine process for pre-clinical drug testing, ensuring only high quality candidates are taken through to clinical trials. Ultimately, we hope this will facilitate the production of more effective medicines that exhibit fewer side effects, enhancing the future treatment of patients.”

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