R-120758, A Novel Triazole Antifungal Agent: In Vivo Antifungal Activity.
Background: R-120758 is a novel triazole antifungal agent with potent and broad-spectrum antifungal activity. The in vivo efficacy of R-120758 was examined and compared with those of the triazole drugs fluconazole (FLCZ) and itraconazole (ITCZ) in murine systemic infection models. Methods: Mice were infected intravenously with fungal suspension. Drugs were administered orally once daily for 10 days. The mortality of the mice was recorded daily. Results: R-120758 delayed mortality dose-dependently against infections with Candida albicans, Aspergillus fumigatus, Aspergillus flavus, and Cryptococcus neoformans. Against infection with C. albicans, R-120758 showed potent efficacy with a 50% effective dose (ED50) of 0.409 mg/kg/dose, which was equal to that of FLCZ and approximately 100-fold lower than that of ITCZ. Against infection with A. fumigatus, R-120758 also showed potent efficacy with an ED50 of 2.38 mg/kg/dose, which was approximately 55- and 38-fold lower than those of FLCZ and ITCZ, respectively. Similarly, R-120758 showed potent efficacy against infection with A. flavus with an ED50 of 3.12 mg/kg/dose, which was approximately 16-fold lower than those of FLCZ and ITCZ. The efficacy of R-120758 against infection with C. neoformans was the greatest among the drugs tested. The ED50 of R-120758 was 3.12 mg/kg/dose, which was approximately 16- and more than 30-fold lower than those of FLCZ and ITCZ, respectively. Conclusion: These results strongly suggest that R-120758 is a promising compound for further evaluation as a new triazole antifungal agent.
Full conference title:
Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy