Development of a Specific Substrate-Inhibitor Panel (Liver-on-a-Chip) for Evaluation of Cytochrome P450 Activity.
Bull Exp Biol Med
; 162(1): 170-174, 2016 Nov.
Article
in En
| MEDLINE
| ID: mdl-27882460
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytochrome P-450 CYP3A
/
Lab-On-A-Chip Devices
/
Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP2C9
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Cytochrome P-450 CYP2C19
Limits:
Humans
Language:
En
Journal:
Bull Exp Biol Med
Year:
2016
Document type:
Article
Affiliation country: