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The Pharmacokinetic Profile of Voriconazole During Continuous High-volume Venovenous Hemofiltration in a Critically Ill Patient

Quintard, Hervé MD*‡; Papy, Emmanuelle PharmD; Massias, Laurent PharmD; Lasocki, Sigismond MD; Arnaud, Philippe MD, PharmD; Desmonts, Jean-Marie MD, PhD; Montravers, Philippe MD, PhD

doi: 10.1097/FTD.0b013e31815c1672
Case Report
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In critically ill patients, dosage adjustment of voriconazole could be helpful when high-volume continuous venovenous hemofiltration is needed. Voriconazole pharmacokinetics were studied in an anuric critically ill patient, under high-volume continuous venovenous hemofiltration, over an interval period after a 4-mg/kg dose of voriconazole. Arterial and effluent voriconazole concentrations were measured after liquid phase extraction using a high-pressure liquid chromatography. The extrapolate area under the curve0-12h of voriconazole was 65 mg/h/L. The total body clearance of voriconazole was 5.4 L/h with a half-life of 16.5 hours and a distribution volume of 128.6 L. The estimated sieving coefficient was 0.58 and the filtration clearance 1.39 L/h. High-volume continuous venovenous hemofiltration could affect voriconazole disposition in contrast with other techniques. Besides, we observed voriconazole accumulation consequence of the saturation of the metabolic clearance resulting from multiple organ failure. Dosage adjustment seems to be required in these conditions, but this observation must be confirmed by a clinical study.

From the *Intensive Care Unit, St. Roche Hospital, Nice, France; †Department of Clinical Pharmacokinetic and Toxicology; and ‡Division of Intensive Care, Bichat Hospital, Paris, France.

Received for publication May 23, 2007; accepted September 20, 2007.

Correspondence: Dr. Hervé Quintard, Intensive Care Unit, St. Roche Hospital, 4 rue Pierre Dévoluy, 06000, Nice, France (e-mail: QUINTARD.H@chu-nice.fr).

© 2008 Lippincott Williams & Wilkins, Inc.