title: In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.
abstract: The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: Hossain
authors.forename: S
authors.initials: S
authors.lastname: Maesaki
authors.forename: K
authors.initials: K
authors.lastname: Mitsutake
authors.forename: H
authors.initials: H
authors.lastname: Kakeya
authors.forename: E
authors.initials: E
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Tomono
authors.forename: T
authors.initials: T
authors.lastname: Tashiro
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008168:Lung / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles