JAC Advance Access originally published online on September 13, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):1085-1090; doi:10.1093/jac/dkm349
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Pharmacokinetics of voriconazole during continuous venovenous haemodiafiltration
1 Department of Internal Medicine 3, Intensive Care Unit 13H1, Medical University Vienna, Vienna, Austria 2 Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria 3 Department of Internal Medicine 1, Division of Infectious Diseases, Medical University Vienna, Vienna, Austria
Received 12 March 2007; returned 29 July 2007; revised 3 June 2007; accepted 15 August 2007
* Corresponding author. Tel: +43-1-40400-4767; Fax: +43-1-40400-4797; E-mail: valentin.fuhrmann{at}meduniwien.ac.at
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 AUC0–12 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, AUC0–12 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.
Keywords: renal replacement therapy , pharmacokinetics , intensive care unit , antimycotic agents
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