Abstract |
A new triazole, Bay R 3783, was compared with ketoconazole, itraconazole, and fluconazole, which were given via the alimentary tract at three dosages, and amphotericin B, which was given at 1 mg/kg intraperitoneally, in murine models of the systemic mycoses coccidioidomycosis, histoplasmosis, and blastomycosis. In a pulmonary coccidioidomycosis model, Bay R 3783, fluconazole, and itraconazole were essentially equally efficacious and more active than ketoconazole in protecting mice against death; but they were inferior to amphotericin B. In a short-term organ load experiment, Bay R 3783 and amphotericin B were equally effective and were more effective than the other drugs in reducing the amount of Coccidioides immitis in the lungs. Against meningocerebral coccidioidomycosis, Bay R 3783, itraconazole, and fluconazole at 25 mg/kg and amphotericin B prevented death only during therapy, with mortalities ensuing shortly thereafter. In mice with systemic histoplasmosis, Bay R 3783 and itraconazole at 25 mg/kg and amphotericin B prevented death in all mice through a 44-day observation period. Clearance of Histoplasma capsulatum from organs was similar in mice treated with Bay R 3783 and itraconazole; this clearance was greater than that in mice treated with ketoconazole and fluconazole but less than that in mice treated with amphotericin B. In mice with systemic blastomycosis, Bay R 3783 at 25 mg/kg yielded 90% survivors at 60 days, which was greater than that achieved with amphotericin B (60%) or itraconazole (30%). Clearance of Blastomyces dermatitidis from the lungs was greatest with Bay R 3783, followed by that with amphotericin B, itraconazole, fluconazole, and ketoconazole, in that order. Therefore, Bay R 3783 showed effectiveness comparable to or exceeding those of itraconazole and fluconazole and exceeding that of ketoconazole against these systemic mycoses in mice.
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Authors | D Pappagianis, B L Zimmer, G Theodoropoulos, M Plempel, R F Hector |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 34
Issue 6
Pg. 1132-8
(Jun 1990)
ISSN: 0066-4804 [Print] United States |
PMID | 2393272
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antifungal Agents
- Triazoles
- Bay R 3783
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Topics |
- Animals
- Antifungal Agents
(pharmacokinetics, therapeutic use)
- Biological Assay
- Blastomycosis
(drug therapy)
- Coccidioidomycosis
(drug therapy)
- Disease Models, Animal
- Female
- Histoplasmosis
(drug therapy)
- Mice
- Microbial Sensitivity Tests
- Survival Rate
- Triazoles
(pharmacokinetics, therapeutic use)
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