Pharmacokinetics of voriconazole during continuous venovenous haemodiafiltration

Objectives: Voriconazole is a new triazole antifungal agent that is frequently used in intensive care patients with severe fungal infections. Continuous venovenous haemodiafiltration (CVVHDF) is an important extracorporal renal replacement therapy in critically ill patients suffering from severe infections and multiple organ failure. This study investigates the pharmacokinetics of voriconazole in anuric patients undergoing CVVHDF. Patients and methods: Pharmacokinetic analysis was performed in nine intensive care patients-one of them with liver cirrhosis-with suspected or proven fungal infection and acute renal failure undergoing CVVHDF who received voriconazole intravenously. The concentration of voriconazole in serum and ultradiafiltrate was determined by HPLC. Results: Mean peak pre-filter voriconazole concentration in eight patients without cirrhosis was 5.9 ± 2.9 mg/L and mean pre-filter trough level was 1.1 ± 0.3 mg/L. Mean elimination half-life, mean volume of distribution, mean AUC_0-12 and mean sieving coefficient were 14.7 ± 6.5 h, 228 ± 42 L, 22.4 ± 3.7 mg·h/L and 0.56 ± 0.16, respectively. The total clearance was 12.9 ± 6.7 L/h and the clearance via CVVHDF was 1.1 ± 0.3 L/h. In the patient with liver cirrhosis, elimination half-life, volume of distribution, AUC_0-12 and sieving coefficient were 52 h, 301 L, 19.8 mg·h/L and 0.31, respectively. Conclusions: Voriconazole should be given without a dosage adaptation in critically ill patients without liver cirrhosis undergoing CVVHDF. However, according to results in one patient, reduction of the maintenance dosing regimen of voriconazole seems to be meaningful in patients with liver cirrhosis.