In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agen t, 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 o f SCH56592, 16 mg/L of fluconatole, 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 lun g 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-inf ected 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.