The efficacy of
ravuconazole, a new
triazole antifungal agent, and the
echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive
aspergillosis. Oral
therapy with
ravuconazole at a dosage of 30 mg/kg of
body weight per day or the
echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for
amphotericin B therapy and untreated controls. Prophylaxis was also studied with
LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge.
Ravuconazole eliminated mortality, cleared aspergillus
antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive
aspergillosis. Although
LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of
ravuconazole and
LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either
drug was seen after 6 days of treatment. Although
LY-303366 showed activity in this rabbit model of invasive
aspergillosis,
ravuconazole was the more active agent, comparable to
amphotericin B. Additional studies are needed to determine the potential of
ravuconazole for use in the treatment of this
infection.