Pharmacokinetics of voriconazole during continuous venovenous haemodiafiltration. 2007

Valentin Fuhrmann, and Peter Schenk, and Walter Jaeger, and Michaela Miksits, and Nikolaus Kneidinger, and Joanna Warszawska, and Ulrike Holzinger, and Reinhard Kitzberger, and Florian Thalhammer
Department of Internal Medicine 3, Intensive Care Unit 13H1, Medical University Vienna, Vienna, Austria. valentin.fuhrmann@meduniwien.ac.at

OBJECTIVE 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. 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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009181 Mycoses Diseases caused by FUNGI. Fungus Diseases,Fungal Diseases,Fungal Infections,Fungus Infections,Disease, Fungal,Disease, Fungus,Diseases, Fungal,Diseases, Fungus,Fungal Disease,Fungal Infection,Fungus Disease,Fungus Infection,Infection, Fungal,Infection, Fungus,Infections, Fungal,Infections, Fungus
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics

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