Comparison of the activity of free and liposomal amphotericin B in vitro and in a model of systemic and localized murine candidiasis.

Abstract

Because of the toxicity of amphotericin B-desoxycholate (AmB-d) during systemic therapy, less toxic forms of AmB, which promise to have a broader therapeutic index, are under investigation. There is, however, no convincing explanation of how such preparations might be made less toxic yet retain their antifungal efficacy. In this study, the antifungal activity of a less toxic, unilamellar liposomal (1) preparation of AmB (AmBisome), which is commercially available in some countries, was compared with conventional AmB-d in vitro and in models of systemic and localized candidiasis in immunosuppressed mice. Results indicate that 1AmB has four to eight times less antifungal activity than AmB-d in all experimental settings tested. Because 1AmB is significantly less active, the therapeutic index of such preparations must be tested clinically before their use can be recommended solely on the basis of toxicity data.