Comparison of amphotericin B and amphotericin B methyl ester: efficacy in murine coccidioidomycosis and toxicity

Abstract

The methyl ester of amphotericin B was compared with the parent compound, amphotericin B, in terms of therapeutic efficacy in experimental murine coccidioidomycosis and of toxicity. Infections were established by intraperitoneal or intratracheal inoculation with arthrospores. The mice were given either intraperitoneal or intravenous injections of drug for 30 days, according to several dosage schedules. At low doses, amphotericin B methyl ester was less effective therapeutically than was amphotericin B; however, at higher doses, amphotericin B was directly lethal and/or nephrotoxic, whereas the methyl ester was therapeutically effective and nontoxic. In contrast to amphotericin B, the methyl ester did not cause either azotemia or histopathologic changes in the kidneys.