Pharmacokinetics of ornidazole in patients with acute viral hepatitis, alcoholic cirrhosis, and extrahepatic cholestasis.
Clin Pharmacol Ther
; 45(4): 373-9, 1989 Apr.
Article
en En
| MEDLINE
| ID: mdl-2702794
ABSTRACT
Pharmacokinetics of ornidazole, a nitroimidazole derivative, was investigated after intravenous injection in 3 groups of 10 patients with different hepatic diseases hepatitis, noncholestatic cirrhosis and extrahepatic cholestasis. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 [alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol] and M4 [3-(2-methyl-5-nitroimidazole 1-yl)-1,2-propane diol] were measured by HPLC assay. As a consequence of a decreased clearance (26% to 48%), the half-life and MRT are increased in all patients by 19% to 38% when compared with healthy volunteers. No clear difference could be established between the different groups. The volume of distribution remains the same in all patients and controls except those suffering from cancer. As previously shown in patients with severe liver cirrhosis, both metabolites accumulate in plasma as a result of decreased elimination; formation is no longer the rate-limiting step of their kinetics. This metabolite accumulation is in part due to decreased biliary excretion and to hepatocellular failure.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ornidazol
/
Colestasis Extrahepática
/
Hepatitis Viral Humana
/
Cirrosis Hepática Alcohólica
/
Nitroimidazoles
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
1989
Tipo del documento:
Article
País de afiliación:
Francia