Pharmacokinetics of ornidazole in patients with severe liver cirrhosis

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Abstract
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 mg/min in patients, whereas apparent Vss 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.