Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole

Objective: To compare the elimination of fluconazole by continuous veno-ven ous haemodiafiltration (CVVHD) and continuous veno-venous haemofiltration ( CVVH) at different dosages. Intervention: Patients received doses of 400 mg (n = 3), 600 mg (n = 1) or 800 mg (n = 2) fluconazole as a short-time infusion once a day. Patients un derwent CVVHD the first day and CVVH the second day. CVVHD and CVVH were pe rformed using an acrylonitrile hollow-fibre filter at a constant blood flow of 90 ml/min and a substitution flow of 1000 ml/h (predilution). During CV VHD, the dialysate flow was 1000 ml/h. Ultrafiltration rates were 1158 +/- 90.5 ml/h during CVVHD and 1167 +/- 81.6 ml/h. Serum and ultrafiltrate/dial ysate concentrations of fluconazole were determined on nine occasions over 24 h. Participants: Six critically ill patients with acute renal failure (ARF) an d serious fungal infection. Results: Extracorporeal clearance (CVVHD 30.5 /- 6.0 ml/min, CVVH 17.5 +/- 4.0 ml/min) and total clearance of fluconazole (CVVHD 37.9 +/- 4.4 ml/min, CVVH 25.3 +/- 6.5 ml/min) were significantly h igher during CVVHD (P < 0.05). During CVVHD, the sieving coefficient (S-CVV HD) was 0.88 (range 0.54-1) and the elimination half-life (t(1/2)) was 14.8 -35.1 h. During CVVH, the S-CVVH was 0.96 (range 0.56-1.02) and t(1/2) was 24.0-51.6 h. Conclusions: A daily dosage of 400-800 mg fluconazole is recommended in the treatment of life-threatening fungal infections in critically ill patients undergoing CVVHD since the clearance of CVVHD may considerably exceed the clearance in patients with normal renal function, which is about 20 ml/min. Drug monitoring is highly recommended for these patients.