Development of a Specific Substrate—Inhibitor Panel (Liver-on-a-Chip) for Evaluation of Cytochrome P450 Activity
- 作者: Zakhariants A.1, Burmistrova O.1, Shkurnikov M.2, Poloznikov A.1, Sakharov D.1
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隶属关系:
- Biocilicum Research and Production Center
- P. A. Hertsen Moscow Oncology Research Institute
- 期: 卷 162, 编号 1 (2016)
- 页面: 170-174
- 栏目: 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
如何引用文章
详细
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.
作者简介
A. Zakhariants
Biocilicum Research and Production Center
编辑信件的主要联系方式.
Email: zakhariants@bioclinicum.com
俄罗斯联邦, Moscow
O. Burmistrova
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
俄罗斯联邦, Moscow
M. Shkurnikov
P. A. Hertsen Moscow Oncology Research Institute
Email: zakhariants@bioclinicum.com
俄罗斯联邦, Moscow
A. Poloznikov
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
俄罗斯联邦, Moscow
D. Sakharov
Biocilicum Research and Production Center
Email: zakhariants@bioclinicum.com
俄罗斯联邦, Moscow
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