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Voriconazole serum concentrations in prophylactically treated acute myelogenous leukaemia patients

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Summary

Antifungal prophylaxis during first remission induction chemotherapy for acute myelogenous leukaemia requires broad spectrum azoles. In a clinical trial, therapeutic drug monitoring (TDM) of antifungal prophylaxis with voriconazole 200 mg bid was evaluated in a population of six patients. High pressure liquid chromatography was applied. Trough levels were obtained 24 h after the last voriconazole dose. Median time of voriconazole exposure prior to sample acquisition was 16 days (range 9–21). The mean voriconazole concentration was 486 μg l−1 and ranged from 136 μg l−1 to 1257 μg l−1. Among possible or probable treatment-related adverse events, elevated liver function tests were the most frequent. Five of six patients developed fever during neutropenia, but none of them developed pulmonary infiltrates or other signs of invasive fungal infection while on voriconazole prophylaxis. Future investigations might aim at identifying drug level thresholds that allow for minimum toxicity and optimum efficacy of antifungal prophylaxis.
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Keywords: Voriconazole; acute myelogenous leukaemia; antifungal prophylaxis; therapeutic drug monitoring

Document Type: Research Article

Affiliations: 1: Klinikum der Universität zu Köln, Klinik I für Innere Medizin, Köln, Germany 2: Institut für Pharmakologie, Universität zu Köln, Köln, Germany 3: Johann Wolfgang Goethe-Universität Frankfurt, Medizinische Klinik II, Frankfurt a.M., Germany 4: Klinikum der Universität zu Köln, Zentrum für Klinische Studien (ZKS) (BMBF 01KN0706), Köln, Germany 5: Institut für Medizinische Statistik, Informatik und Epidemiologie der Universität zu Köln, Köln, Germany

Publication date: May 1, 2011

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