title: Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of pulmonary aspergillosis.
abstract: The efficacy of FK463, a novel water-soluble lipopeptide, was evaluated in mouse models of pulmonary aspergillosis and was compared with that of amphotericin B (AMPH-B). In the pulmonary aspergillosis models induced by intranasal inoculation, FK463 exhibited good efficacy, with 50% effective doses in the range of 0. 26 to 0.51 mg/kg of body weight; these values were comparable to those of AMPH-B. In an Aspergillus target organ assay with immunosuppressed mice, under conditions of constant plasma levels of FK463, using a subcutaneously implanted osmotic pressure pump, a significant reduction in viable fungal cells was observed at plasma FK463 levels of 0.55 to 0.80 microgram/ml or higher. We conclude that FK463 is highly effective in the treatment of pulmonary aspergillosis in this animal model. These results indicate that FK463 may be a potent parenterally administered antifungal agent for pulmonary aspergillosis.
authors.affiliation: Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Wakai
authors.forename: T
authors.initials: T
authors.lastname: Nakai
authors.forename: K
authors.initials: K
authors.lastname: Hatano
authors.forename: T
authors.initials: T
authors.lastname: Ushitani
authors.forename: F
authors.initials: F
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Tawara
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: F
authors.initials: F
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kuwahara
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use*; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000382:microbiology; D000077551:Micafungin; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077551:Micafungin