In vitro and in vivo antifungal activities of
D0870 were evaluated in comparison with those of
fluconazole.
D0870, which is the R-enantiomer of ICI195,739, was found to be the mycologically active enantiomer by comparing the activities of
D0870 with those of M16355 (S-enantiomer of ICI195,739).
D0870 showed a broad spectrum of antifungal activity and MICs and minimum
antibiotic concentrations 4- to 2,000-fold lower in synthetic
amino acid medium (fungal)
agar than those of
fluconazole for various fungi. Although MICs of
D0870 were affected by variation of the test conditions, such as type of medium, inoculum size of fungi, supplementation with
fetal bovine serum, and pH of medium, they were consistently much lower than those of
fluconazole under any condition. In vivo activities of
D0870 in the systemic
infection models with Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in normal mice and in the mice immunosuppressed with
cyclophosphamide or
cortisone acetate were 2- to 7-fold and 3- to 89-fold greater than those of
fluconazole, respectively. In these
infection models in immunosuppressed mice, the therapeutic efficacy of
D0870 was almost equivalent to that in normal mice, whereas the efficacy of
fluconazole was 2- to 50-fold lower than that in normal mice.