Factors influencing rates and clearance in P450-mediated reactions: QSARs for substrates of the xenobiotic-metabolizing hepatic microsomal P450s.
Toxicology
; 170(1-2): 45-53, 2002 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-11750082
ABSTRACT
Various contributory factors associated with the kinetics of cytochrome P450-mediated catalytic activity and the metabolic clearance of drug substrates are discussed and evaluated, based on literature data and physicochemical parameters. Quantitative relationships between molecular structure and biological activity for several series of P450 substrates are presented which point to certain commonalities in P450-catalyzed reactions. In particular, it appears that frontier orbital energies are especially important for the estimation of reaction rates and clearance for many P450 substrates, although occasionally these have to be combined with other descriptors, such as compound lipophilicity (in the form of logP or logD(74)).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microssomos Hepáticos
/
Xenobióticos
/
Sistema Enzimático do Citocromo P-450
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article