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

Abstract.

Objective: To compare the elimination of fluconazole by continuous veno–venous 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 underwent CVVHD the first day and CVVH the second day. CVVHD and CVVH were performed 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 CVVHD, 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/dialysate concentrations of fluconazole were determined on nine occasions over 24 h. Participants: Six critically ill patients with acute renal failure (ARF) and 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 higher during CVVHD (P<0.05). During CVVHD, the sieving coefficient (S_CVVHD) 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.