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We evaluated the disposition of metronidazole and its two major metabolites in 14 critically ill patients with liver and renal dysfunction. Patients received 500 mg of metronidazole iv for periods of 2-13 days and were studied either during therapy or after their final dose. The metronidazole half-life ranged between 4.95 and 42.4 h. Patients with obstructive liver disease exhibited the longest half-lives (9.15-42.4 h) and lowest clearances (0.281-1.17 ml/min/kg). The presence of obstructive liver disease or renal impairment appeared to prolong the elimination of the hydroxymetabolite. We conclude that the pharmacokinetics of metronidazole and its metabolites are significantly affected in critically ill patients with liver and renal dysfunction.
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