Open AccessIn Vitro and In Vivo Activities of SCH 56592 (Posaconazole), a New Triazole Antifungal Agent, against Aspergillus and Candida
Author(s) -
Anthony Cacciapuoti,
David Loebenberg,
Erik Corcoran,
Fred Menzel,
Eugene L. Moss,
Christine Norris,
Monika Michalski,
Kimberly Raynor,
Judith Halpern,
Cara Mendrick,
Brian M. Arnold,
Barry Antonacci,
Raulo Parmegiani,
T. Yarosh-Tomaine,
George H. Miller,
R S Hare
Publication year - 2000
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.44.8.2017-2022.2000
Subject(s) - posaconazole , itraconazole , fluconazole , aspergillus fumigatus , microbiology and biotechnology , aspergillus flavus , candida albicans , aspergillus , in vivo , pharmacology , triazole , cryptococcus neoformans , cryptococcosis , cryptococcus , biology , chemistry , antifungal , organic chemistry
SCH 56592 (posaconazole), a new triazole antifungal agent, was tested in vitro, and its activity was compared to that of itraconazole against 39Aspergillus strains and to that of fluconazole against 275Candida and 9Cryptococcus strains. The SCH 56592 MICs forAspergillus ranged from ≤0.002 to 0.5 μg/ml, and those of itraconazole ranged from ≤0.008 to 1 μg/ml. The SCH 56592 MICs forCandida andCryptococcus strains ranged from ≤0.004 to 16 μg/ml, and those of fluconazole ranged from ≤0.062 to >64 μg/ml. SCH 56592 showed excellent activity againstAspergillus fumigatus andAspergillus flavus in a pulmonary mouse infection model. When administered therapeutically, the 50% protective doses (PD50 s) of SCH 56592 ranged from 3.6 to 29.9 mg/kg of body weight, while the PD50 s of SCH 56592 administered prophylactically ranged from 0.9 to 9.0 mg/kg; itraconazole administered prophylactically was ineffective (PD50 s, >75 mg/kg). SCH 56592 was also very efficacious against fluconazole-susceptible, -susceptible dose-dependent, or -resistantCandida albicans strains in immunocompetent or immunocompromised mouse models of systemic infection. The PD50 s of SCH 56592 administered therapeutically ranged from 0.04 to 15.6 mg/kg, while the PD50 s of SCH 56592 administered prophylactically ranged from 1.5 to 19.4 mg/kg. SCH 56592 has excellent potential for therapy against seriousAspergillus orCandida infections.