In vitro metabolism and in vivo pharmacokinetics of quinoline 3-carboxamide derivatives in various species.
Xenobiotica
; 35(3): 293-304, 2005 Mar.
Article
en En
| MEDLINE
| ID: mdl-16019952
ABSTRACT
The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent compounds in the mouse. The therapeutic effect seen in the acute EAE mouse model for these related compounds seems dependent on the high exposure of parent compound rather than formation of any potentially active metabolites.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microsomas Hepáticos
/
Hidroxiquinolinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Xenobiotica
Año:
2005
Tipo del documento:
Article
País de afiliación:
Suecia