Cytochrome P450 inhibition assays using traditional and fluorescent substrates.
Curr Protoc Pharmacol
; Chapter 7: Unit7.11, 2007 Dec.
Article
in En
| MEDLINE
| ID: mdl-21948171
ABSTRACT
A key liability in transitioning a new chemical entity (NCE) to a development candidate is NCE-related inhibition (or induction) of cytochrome P450 enzymes, a superfamily of heme-containing oxygenases that are the major route of first-pass metabolism for the majority of marketed drugs. The drawback of a drug/NCE that modulates CYP450 enzyme activity occurs when the compound is co-administered with another drug that relies on the same P450 enzyme for its metabolism. This could result in overdose of the second drug in the case of inhibition, or more rapid metabolism of one or both drugs accompanied by loss of efficacy in the case of enzyme induction. Screening for the inhibition of CYP450 enzymes is now routine in the early stages of evaluating NCEs. This unit describes two inhibition assays using traditional and fluorescent substrates.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enzyme Inhibitors
/
Cytochrome P-450 Enzyme Inhibitors
Language:
En
Journal:
Curr Protoc Pharmacol
Year:
2007
Document type:
Article
Affiliation country: