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  • Title: Pharmacokinetics of diazepam in the rat: influence of an experimentally induced hepatic injury.
    Author: Diaz-Garcia JM, Oliver-Botana J, Fos Galve D.
    Journal: Eur J Drug Metab Pharmacokinet; 1991; Spec No 3():94-101. PubMed ID: 1820943.
    Abstract:
    The aim of this study was to compare the pharmacokinetics of diazepam in normal rats and rats with a carbon tetrachloride-induced hepatic cirrhosis after intravenous and oral administration of the drug (4 mg/Kg). When animals are pretreated with this hepatotoxic agent, a significant prolongation in plasma half-life of diazepam is observed, due more to an increase in volume of distribution rather than to a decrease in clearance. Our findings confirm that diazepam is highly extracted by the liver of the rat. This parameter is not affected by the hepatotoxic agent, but probably there is a saturation of the hepatic enzyme activity when the drug is orally administered at the dose of 4 mg/Kg. Diazepam binds to a high degree to plasma proteins in normal and damaged rats, though in the last case a significant increase in the unbound fraction of drug in plasma is observed. Pretreatment of rats with Cl4C does not produce any change in distribution of diazepam into erythrocytes.
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