Disposition and removal of metronidazole in patients undergoing haemodialysis

The pharmacokinetics and haemodialysis clearance of metronidazole were investigated in four renal failure patients after a single 500 mg intravenous dose and in two renal failure patients on continuous treatment with metronidazole. During dialysis, the volume of distribution of metronidazole was 0.60 +/- 0.04 l/kg, total clearance was 196.0 +/- 60.6 ml/min and the elimination half-life had an harmonic mean of 2.14 h. Extraction across the dialyser was 51.5 +/- 7.8% and was limited to the distribution of drug in plasma water. Dialysis clearance was 125.0 +/- 32.7 ml/min, which represented 62 +/- 6% of total clearance and was 1.75 times the sum of the other clearance mechanisms. The hydroxy metabolite was extracted and cleared by the dialyser to the same degree as metronidazole itself. During the 4 h-dialysis 44.9 +/- 2.6% of the dose was removed by the dialyser in the four patients administered a single dose. Metronidazole is efficiently cleared and extensively removed by dialysis, and therefore dosage adjustments and alterations in the timing of dosage administration are essential in patients undergoing haemodialysis.