Effect of continuous venovenous haemofiltration and haemodiafiltration on the elimination of fluconazole in patients with acute renal failure

The elimination of fluconazole was studied in six patients with acute renal Failure undergoing continuous venovenous haemofiltration (CVVH) for 24 h, continuous venovenous haemodiafiltration (CVVHD) 1 L/h for 24 h and CVVHD 2 L/h for 24 h. Fluconazole 200 mg once daily was given intravenously on three successive days and the concentrations of fluconazole in serum, ultrafiltrate/dialysate and urine were determined for 24 h after each dose. The half-life of fluconazole in patients during CVVH (83.5 +/- 30.1 h; mean +/- s.o.) was significantly (P < 0.05) longer than that during CVVHD 1 L/h (30.4 +/- 5.0 h) or CVVHD 2 L/h (21.8 +/- 3.5 h). The total fluconazole clearance was 0.57 +/- 0.16 L/h, 1.50 +/- 0.24 L/h and 1.85 +/- 0.17 L/h in CVVH, CVVHD 1 Uh and CVVHD 2 Uh, respectively, and there was a significant difference (P < 0.05) between all these treatments. Daily renal excretion of fluconazole was minimal, ranging from 0.002 mg to 11.2 mg in different patients with different treatment modes. The methods tested increased the elimination of the unchanged drug 20- to 400-fold in patients with acute renal failure. Patients undergoing CVVHD therapy with a dialysis flow rates of 1 or 2 Uh should be treated with a daily dose of at least 200 mg of fluconazole to maintain therapeutic drug concentrations. However, in patients on CVVH therapy smaller doses of fluconazole may be enough.