Amphotericin-B colloidal dispersion. A review of its use against systemic fungal infections and visceral leishmaniasis.

Abstract

Formulation of amphotericin B with sodium cholesteryl sulphate alters the pharmacokinetic properties of the drug, particularly reducing its distribution to the kidneys. The antifungal activity in vitro of amphotericin B colloidal dispersion (ABCD) is similar to that of conventional amphotericin B (C-AmB) against true pathogenic organisms including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides species and the opportunistic organisms such as Candida and Cryptococcus species. In animal models, ABCD was generally less effective than an identical dose of C-AmB, but overall was more effective because of its improved therapeutic index. Although ABCD appeared to be more effective than C-AmB in resolving infection and improving survival in patients with proven or probable invasive aspergillosis, the retrospective design of the study and the greater prevalence of neutropenia in patients treated with the conventional formulation necessitate cautious interpretation of the results. ABCD has been effective and seldom caused nephrotoxicity in patients with fungal infection who had previously failed to adequately respond or had developed renal toxicity with C-AmB. Similarly, ABCD was effective in patients with proven or suspected fungal infection after bone marrow transplantation. Preliminary results from a pilot study comparing ABCD and C-AmB in patients with neutropenia and persistent fever reported similar response rates with both formulations. ABCD is an effective treatment for visceral leishmaniasis in immunocompetent patients. In 1 study, about 12% of ABCD recipients discontinued the drug because of adverse events; infusion-related events were the most common cause of discontinuation. The renal tolerability of ABCD is better than that of C-AmB. ABCD appears to be an effective alternative to conventional amphotericin B in patients with invasive aspergillosis or visceral leishmaniasis and in those with proven or suspected systemic fungal infection who are intolerant of the conventional formulation or have pre-existing renal impairment. Preliminary data also suggest that ABCD is an alternative to C-AmB when used empirically in patients with neutropenia and fever. Nevertheless, the efficacy of ABCD compared with that of the conventional formulation has yet to be adequately demonstrated and the role of ABCD relative to that of liposomal and other lipid-based formulations has not been determined. ABCD, like other lipid-based and liposomal formulations of amphotericin B, has been designed to deliver the active drug to the target site, while reducing renal toxicity. The aim of increasing the therapeutic index compared with C-AmB has been achieved.