NDLI: Bronchopulmonary Disposition of Intravenous Voriconazole and Anidulafungin Given in Combination to Healthy Adults▿

Content Provider	PubMed Central
Author	Crandon, Jared L. Anne, Banevicius Mary Fang, Annie F. Crownover, Penelope H. Knauft, R. Fredrick Pope, J. Samuel Russomanno, John H. Shore, Eric Nicolau, David P. Kuti, Joseph L.
Copyright Year	2009
Abstract	Voriconazole and anidulafungin in combination are being investigated for use for the treatment of pulmonary aspergillosis. We determined the pulmonary disposition of these agents. Twenty healthy participants received intravenous voriconazole (at 6 mg/kg of body weight every 12 h [q12h] on day 1 and then at 4 mg/kg q12h) and anidulafungin (200 mg on day 1 and then 100 mg every 24 h) for 3 days. Five participants each were randomized for collection of bronchoalveolar lavage samples at times of 4, 8, 12, and 24 h. Drug penetration was determined by the ratio of the total drug area under the concentration-time curve during the dosing interval (AUC0-τ) for epithelial lining fluid (ELF) and alveolar macrophages (AM) to the total drug AUC0-τ in plasma. The mean (standard deviation) half-life and AUC0-τ were 6.9 (2.1) h and 39.5 (19.8) μg·h/ml, respectively, for voriconazole and 20.8 (3.1) h and 101 (21.8) μg·h/ml, respectively, for anidulafungin. The AUC0-τ values for ELF and AM were 282 and 178 μg·h/ml, respectively, for voriconazole, and 21.9 and 1,430 μg·h/ml, respectively, for anidulafungin. This resulted in penetration ratios into ELF and AM of 7.1 and 4.5, respectively, for voriconazole and 0.22 and 14.2, respectively, for anidulafungin. The mean total concentrations of both drugs in ELF and AM at 4, 8, 12, and 24 h remained above the MIC90/90% minimum effective concentration for most Aspergillus species. In healthy adult volunteers, voriconazole achieved high levels of exposure in both ELF and AM, while anidulafungin predominantly concentrated in AM.
Related Links	http://dx.doi.org/10.1128/aac.01042-09
Ending Page	5107
Page Count	6
Starting Page	5102
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	12
Volume Number	53
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2009-12-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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