AMPHOTERICIN-B AND AMPHOTERICIN-B METHYL-ESTER ASCORBATE .1. CHEMOTHERAPEUTIC ACTIVITY AGAINST CANDIDA-ALBICANS, CRYPTOCOCCUS-NEOFORMANS, AND BLASTOMYCES-DERMATITIDIS IN MICE

Amphotericin B methyl ester (AME) was reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME was proposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the 2 polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with C. albicans, C. neoformans and B. dermatitidis. Treatment consisted of 2 or more doses of each drug given by the i.v. route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections. Amphotericin B had a higher therapeutic ratio for all infections studied than did AME.