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Expert Opin Drug Metab Toxicol. 2007 Jun;3(3):321-9.

In vitro approaches to investigate mechanism-based inactivation of CYP enzymes.

Author information

1
Flinders University and Flinders Medical Centre, Department of Clinical Pharmacology, Bedford Park, 5042, Adelaide, Australia. tom.polasek@flinders.edu.au

Abstract

Mechanism-based inactivation (MBI) of human drug-metabolising CYP enzymes is an important consideration in the preclinical ADME evaluation of new drug candidates. In this report, the in vitro approaches used to investigate MBI of CYP enzymes are described, with an emphasis on the characterisation required to assess potential drug-drug interactions. Recent disparities in MBI data between in vitro test systems are also reviewed, highlighting the limitations of Escherichia coli-expressed human recombinant CYP in the prediction of drug-drug interactions that arise via MBI.

PMID:
17539741
DOI:
10.1517/17425255.3.3.321
[Indexed for MEDLINE]

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