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Bull Exp Biol Med. 2016 Nov;162(1):170-174. Epub 2016 Nov 23.

Development of a Specific Substrate-Inhibitor Panel (Liver-on-a-Chip) for Evaluation of Cytochrome P450 Activity.

Author information

1
Biocilicum Research and Production Center, Moscow, Russia. zakhariants@bioclinicum.com.
2
Biocilicum Research and Production Center, Moscow, Russia.
3
P. A. Hertsen Moscow Oncology Research Institute, Moscow, Russia.

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.

KEYWORDS:

HepaRG; biotransformation; liver cell model; liver-on-a-chip; preclinical in vitro studies

PMID:
27882460
DOI:
10.1007/s10517-016-3567-z
[Indexed for MEDLINE]

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