Development of a Specific Substrate—Inhibitor Panel (Liver-on-a-Chip) for Evaluation of Cytochrome P450 Activity
- Authors: Zakhariants A.A.1, Burmistrova O.A.1, Shkurnikov M.Y.2, Poloznikov A.A.1, Sakharov D.A.1
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Affiliations:
- Biocilicum Research and Production Center
- P. A. Hertsen Moscow Oncology Research Institute
- Issue: Vol 162, No 1 (2016)
- Pages: 170-174
- Section: Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
- URL: https://journals.rcsi.science/0007-4888/article/view/237997
- DOI: https://doi.org/10.1007/s10517-016-3567-z
- ID: 237997
Cite item
Abstract
We developed a cytochrome P450 substrate—inhibitor panel for preclinical in vitro evaluation of drugs in a 3D histotypical microfluidic cell model of human liver (liver-on-a-chip technology). The concentrations of substrates and inhibitors were optimized to ensure reliable detection of the principal metabolites by HPLC—mass-spectroscopy. The selected specific substrate—inhibitor pairs, namely bupropion/2-phenyl-2-(1-piperidinyl)propane) for evaluation of CYP2B6B activity, tolbutamide/sulfaphenazole for CYP2C9, omeprazole/(+)-N-benzylnirvanol for CYP2C19, and testosterone/ketoconazole for CYP3A4, enable reliable evaluation of the drug metabolism pathway. In contrast to animal models characterized by species-specific expression profile and activity of cytochrome P450 isoforms, our in vitro model reflects the metabolism of human hepatocytes in vivo.
About the authors
A. A. Zakhariants
Biocilicum Research and Production Center
Author for correspondence.
Email: zakhariants@bioclinicum.com
Russian Federation, Moscow
O. A. Burmistrova
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
Russian Federation, Moscow
M. Y. Shkurnikov
P. A. Hertsen Moscow Oncology Research Institute
Email: zakhariants@bioclinicum.com
Russian Federation, Moscow
A. A. Poloznikov
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
Russian Federation, Moscow
D. A. Sakharov
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
Russian Federation, Moscow