title: In vitro and in vivo activities of CS-758 (R-120758), a new triazole antifungal agent.
abstract: The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 microg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.
authors.affiliation: Biological Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan. ykamai@shina.sankyo.co.jp
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kamai
authors.forename: Tamako
authors.initials: T
authors.lastname: Harasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohya
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Shogo
authors.initials: S
authors.lastname: Kuwahara
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects; D004195:Disease Models, Animal; D051379:Mice; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C453343:R-120758