Metronidazole: pharmacokinetic observations in severely ill patients

Single and multiple dose pharmacokinetics of metronidazole and its two major metabolites were studied in ten patients. Patients with hepatic insufficiency had longer average serum half-life of metronidazole (11.2 h) than individuals with normal liver and kidney function (5.9 h) or isolated moderate renal impairment (6.5 h). Patients with hepatic disorder presented larger areas under the serum concentration curve, lower serum clearances and a tendency to more rapidly rising trough values of metronidazole. In patients with renal insufficiency trough values of the hydroxy metabolite seemed to rise faster and serum half-life was prolonged. The acetic acid metabolite was detected in serum of all patients with renal dysfunction but only in half of those with normal renal function and then at lower levels. A reduced 24-h total urinary recovery of metronidazole among patients with renal disorder was explained by a decreased excretion of hydroxy metabolite. The kinetics of metronidazole itself seem not to be influenced by renal impairment while the elimination rate of metabolites is reduced. The decreased clearance of the drug in patients with hepatic dysfunction makes a dose reduction in this patient group advisable.