EFFECT OF CONTINUOUS VENOVENOUS HEMOFILTRATION AND HEMODIAFILTRATION 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 2 4 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 fluco nazole 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) lo nger 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) b etween all these treatments. Daily renal excretion of fluconazole was minimal, ranging from 0.002 mg to 11.2 mg in different patients with d ifferent treatment modes. The methods tested increased the elimination of the unchanged drug 20- to 400-fold in patients with acute renal fa ilure. 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 f luconazole to maintain therapeutic drug concentrations. However, in pa tients on CVVH therapy smaller doses of fluconazole may be enough.