Metronidazole Pharmacokinetics in Patients with Hepatic Encephalopathy

Abstract

The pharmacokinetics of metronidazole and its major metabolites was investigated in eight patients with liver cirrhosis and coma of grade 2 to 4 and in eight healthy controls. In the coma patients the systemic clearance of metronidazole was reduced (29 ± 10 versus 83 ± 14 ml/min, mean ± SD; p < 0.001) and the elimination half-life prolonged (20 ± 9 versus 7.3 ± 0.9 h; p < 0.001), whereas the volume of distribution at steady state was unchanged (44 ± 9 versus 48 ± 7 1) as compared with the healthy controls. Investigation of the major elimination pathways of metronidazole showed that the decreased rate of elimination in the patients was mainly due to impaired hepatic drug oxidation. In four patients therapeutic plasma concentrations were achieved during 6 day' treatment with 500 mg metronidazole per 24 or 48 h.

Key Words:

• Drug metabolism
• liver cirrhosis
• liver coma
• metronidazole metabolism