Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections.

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.

• 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)

Chemical References

• Antifungal Agents
• Imidazoles
• Amphotericin B
• luliconazole

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