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-venous haemodiafiltration (CVVHD) and continuous veno-venous haemofiltration (CVVH) at different dosages.


METHODS
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.


METHODS
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 (t1/2) was 14.8-35.1 h. During CVVH, the S(CVVH) was 0.96 (range 0.56-1.02) and t1/2 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.
Muhl
E
E
Department of Surgery, Medical University of Luebeck, Germany. 045091252-0001@t-online.de
Martens
T
T
Iven
H
H
Rob
P
P
Bruch
H P
HP
D058186:Acute Kidney Injury / Q000378:metabolism; D000368:Aged; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid; D002177:Candidiasis / Q000378:metabolism; D016638:Critical Illness; D005112:Extracorporeal Circulation; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics*; D006207:Half-Life; D017583:Hemodiafiltration; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged
D000935:Antifungal Agents; D015725:Fluconazole