Abstract |
In vitro and in vivo anti-Candida albicans and anti-Aspergillus fumigatus activities of NND-502, a new imidazole-antimycotic, were compared with those of fluconazole (FCZ), itraconazole (ITZ) and/or amphotericin B (AmB). NND-502 exhibited strong in vitro antifungal activity against both fungal species; its MIC against C. albicans was 1-4 times lower than that of FCZ, and its MIC against A. fumigatus was at least 60-2000 times lower than that of ITZ and AmB. In vivo antifungal treatments with each drug were initiated 1 h after inoculation in the experimental models, so that antifungal potential reflected prophylactic activity rather than therapeutic activity. The oral regimen of NND-502 in a murine model of systemic C. albicans infection was much less effective than that of FCZ. In vivo anti-A. fumigatus activity of oral NND-502 in a murine model of systemic infection was apparently superior to that of FCZ and ITZ in terms of prolonging survival. In addition to the murine model of systemic aspergillosis, intravenous NND-502 was shown to be highly effective in a rat model of pulmonary aspergillosis compared with intravenous AmB; 90% of animals survived at a dose of 2.5 mg/kg per day of NND-502 while only 30% of animals escaped death when 5 mg/kg per day of AmB was used. This potent efficacy of NND-502 was also confirmed in a sublethal challenge study in which the administration of the agent at a dose as low as 1.25 mg/kg per day resulted in the significant reduction of organisms in the lung; no comparable effect of AmB was found.
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Authors | Y Niwano, N Kuzuhara, Y Goto, Y Munechika, H Kodama, K Kanai, M Yoshida, T Miyazaki, H Yamaguchi |
Journal | International journal of antimicrobial agents
(Int J Antimicrob Agents)
Vol. 12
Issue 3
Pg. 221-8
(Aug 1999)
ISSN: 0924-8579 [Print] Netherlands |
PMID | 10461840
(Publication Type: Journal Article)
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Chemical References |
- Antifungal Agents
- Imidazoles
- Amphotericin B
- luliconazole
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Topics |
- Amphotericin B
(therapeutic use)
- Animals
- Antifungal Agents
(pharmacology, therapeutic use)
- Aspergillosis
(drug therapy, microbiology)
- Aspergillus fumigatus
(drug effects)
- Candida albicans
(drug effects)
- Candidiasis
(drug therapy, microbiology)
- Imidazoles
(pharmacology, therapeutic use)
- Lung Diseases
(drug therapy, microbiology)
- Male
- Microbial Sensitivity Tests
- Rats
- Rats, Sprague-Dawley
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