Pharmacokinetics of ornidazole in patients with severe liver cirrhosis.
Pharmacokinetics of ornidazole, a nitroimidazole derivative, was studied after intravenous injection in 10 patients with severe alcoholic cirrhosis and 10 healthy volunteers. 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. The t1/2 of ornidazole was 14.1 +/- 0.5 hours for normal subjects and 21.9 +/- 2.9 hours for patients with cirrhosis. Mean plasma clearance was 50.6 +/- 2.1 ml/min in control subjects and 34.9 +/- 4.9 ml/min in patients, whereas apparent V SS was not modified in hepatic insufficiency. In healthy volunteers, M1 and M4 levels are well below levels of the parent drug; in cirrhosis both metabolites accumulate in plasma as a result of decreased elimination. Hepatic cirrhosis prolongs ornidazole elimination, and to avoid cumulation the interval between repeated doses could be doubled.
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007700:Kinetics; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D009593:Nitroimidazoles / Q000097:blood*; D009950:Ornidazole / Q000097:blood*
D009593:Nitroimidazoles; D009950:Ornidazole