Pharmacokinetics of diazepam in the rat: influence of a carbon tetrachloride-induced hepatic injury.
J Pharm Sci
; 81(8): 768-72, 1992 Aug.
Article
em En
| MEDLINE
| ID: mdl-1403721
ABSTRACT
The pharmacokinetics of diazepam in normal rats and in rats pretreated with carbon tetrachloride to induce hepatic cirrhosis (cirrhotic rats) was studied after intravenous and oral administration of the drug (4 mg/kg). Animals pretreated with this hepatotoxic agent showed a significant prolongation in the half-life of diazepam in plasma that is due more to an increase in volume of distribution rather than to a decrease in clearance. This study confirmed that diazepam was highly extracted by the rat liver and was not affected by the hepatotoxic agent, although there probably was a saturation of the activity of the cytochrome P450 enzyme when the drug was administered orally. Diazepam binds to plasma proteins to a high degree in both normal and cirrhotic rats; however, in the latter, a significant increase in the fraction of unbound drug in plasma was observed. Pretreatment of rats with carbon tetrachloride did not produce any change either in the distribution of diazepam into erythrocytes or in the disposition of the metabolite desmethyldiazepam.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Tetracloreto de Carbono
/
Diazepam
/
Fígado
/
Hepatopatias
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article