Metronidazole pharmacokinetics in patients with acute renal failure

The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 ±0.13 I/kg (mean ±s.d.), elimination half-life was 9.9 ±2.5 h and total plasma clearance was 55.5 ± 17.7 ml/min. Renal clearance was almost non-existent (1.4± 1.4 ml/min), whereas non-renal clearance was 54.0 ± 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.;3 ±3.8 mg/1, the hydroxy metabolite were 17.4 ±2.0 mg/1 and the acetic acid metabolite were 1.2 ±0.8 mg/1. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.