Determination of In Vitro Cytochrome P450 Induction Potential Using Cryopreserved Human Hepatocytes

2021 ◽  
pp. 193-215
Author(s):  
Susan Wong
Keyword(s):  
Cytochrome P450 ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction

Comparison of Immortalized Fa2N-4 Cells and Human Hepatocytes as in Vitro Models for Cytochrome P450 Induction

2008 ◽  
Vol 36 (6) ◽  
pp. 1046-1055 ◽  
Author(s):  
Niresh Hariparsad ◽  
Brian A. Carr ◽  
Raymond Evers ◽  
Xiaoyan Chu
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Models ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction

Utility of Long-Term Cultured Human Hepatocytes as an in Vitro Model for Cytochrome P450 Induction

2006 ◽  
Vol 35 (2) ◽  
pp. 215-220 ◽  
Author(s):  
Georgina Meneses-Lorente ◽  
Christine Pattison ◽  
Claire Guyomard ◽  
Christophe Chesné ◽  
Robert Heavens ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

CRYOPRESERVED HUMAN HEPATOCYTES AS ALTERNATIVE IN VITRO MODEL FOR CYTOCHROME P450 INDUCTION STUDIES

2003 ◽  
Vol 39 (7) ◽  
pp. 283 ◽  
Author(s):  
MARTHA GARCIA ◽  
JOSEPH RAGER ◽  
QING WANG ◽  
ROBERT STRAB ◽  
ISMAEL J. HIDALGO ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

Evaluation of Cytochrome P450 Activities in Human Hepatocytes In Vitro

2011 ◽  
pp. 87-97 ◽  
Author(s):  
María José Gómez-Lechón ◽  
Agustín Lahoz ◽  
José V. Castell ◽  
María Teresa Donato
Keyword(s):  
Cytochrome P450 ◽  
Human Hepatocytes

scholarly journals In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-N-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 818
Author(s):  
Ju-Hyun Kim ◽  
Sunjoo Kim ◽  
Jaesin Lee ◽  
Sangwhan In ◽  
Yong-Yeon Cho ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
High Resolution Mass Spectrometry ◽  
Human Hepatocytes ◽  
Liquid Chromatography Mass Spectrometry ◽  
Metabolic Characteristics ◽  
Hepatic Extraction Ratio ◽  
Potent Agonist

25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography–high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, O-demethylation, bis-O-demethylation, N-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse.

scholarly journals Application of a Substrate Cocktail Approach in the Assessment of Cytochrome P450 Induction Using Cultured Human Hepatocytes

2012 ◽  
Vol 18 (2) ◽  
pp. 199-210 ◽  
Author(s):  
Robert D. Pelletier ◽  
W. George Lai ◽  
Y. Nancy Wong
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
High Throughput ◽  
Viable Cell ◽  
Human Hepatocytes ◽  
Cyp Induction ◽  
Cell Counts ◽  
Cytochrome P450 Induction ◽  
Fold Induction ◽  
Cocktail Approach

Induction of the cytochrome P450 (CYP) family of enzymes by coadministered compounds can result in drug-drug interactions, as in the case of the coadministration of rifampicin with many CYP3A substrates, including midazolam. Identification of potential drug-drug interactions due to CYP induction during drug discovery is critical. We present a substrate cocktail method that was applied to assess the induction of CYP1A, CYP2B6, CYP2C9, and CYP3A using a 96-well high-throughput format. Viable cell counts were determined using a high-content screening system to normalize activities. Substrate cocktail incubations demonstrated a similar fold induction for known inducers as compared with discrete probe incubations. The system was further validated by determining the induction potency of rifampicin. The Emax and EC50 values in two separate lots of hepatocytes for CYP3A induction by rifampicin in a 96-well format were similar when discrete probe was compared with the probe cocktail. This system has been demonstrated to be suitable for high-throughput assessments of CYP induction.

Determination of cytochrome P450 1A2 and cytochrome P450 3A4 induction in cryopreserved human hepatocytes

2004 ◽  
Vol 67 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Dirk Roymans ◽  
Cis Van Looveren ◽  
Angelique Leone ◽  
J.Brandon Parker ◽  
Michael McMillian ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Hepatocytes ◽  
Cytochrome P450 3A4 ◽  
Cytochrome P450 1A2
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