title: The pharmacokinetic profile of voriconazole during continuous high-volume venovenous hemofiltration in a critically ill patient.
abstract: 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 curve(0-12h) 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.
authors.affiliation: Intensive Care Unit, St. Roche Hospital, Nice, France. QUINTARD.H@chu-nice.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Quintard
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Papy
authors.forename: Laurent
authors.initials: L
authors.lastname: Massias
authors.forename: Sigismond
authors.initials: S
authors.lastname: Lasocki
authors.forename: Philippe
authors.initials: P
authors.lastname: Arnaud
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Desmonts
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000628:therapy*; D000368:Aged; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy*; D016638:Critical Illness; D017809:Fatal Outcome; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole