AMPHOTERICIN-B COLLOIDAL DISPERSION - A REVIEW OF ITS USE AGAINST SYSTEMIC FUNGAL-INFECTIONS AND VISCERAL LEISHMANIASIS

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 ampho tericin B colloidal dispersion (ABCD) is similar to that of convention al amphotericin B (C-AmB) against true pathogenic organisms including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides species a nd the opportunistic organisms such as Candida and Cryptococcus specie s. In animal models, ABCD was generally less effective than an identic al dose of C-AmB, but overall was more effective because of its improv ed 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 treat ed with the conventional formulation necessitate cautious interpretati on of the results. ABCD has been effective and seldom caused nephrotox icity in patients with fungal infection who had previously failed to a dequately respond or had developed renal toxicity with C-AmB. Similarl y, ABCD was effective in patients with proven or suspected fungal infe ction after bone marrow transplantation. Preliminary results from a pi lot study comparing ABCD and C-AmB in patients with neutropenia and pe rsistent fever reported similar response rates with both formulations. ABCD is an effective treatment for visceral leishmaniasis in immunoco mpetent patients. In 1 study, about 12% of ABCD recipients discontinue d tba 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 alternat ive to conventional amphotericin B in patients with invasive aspergill osis or visceral leishmaniasis and in those with proven or suspected s ystemic fungal infection who are intolerant of the conventional formul ation or have pre-existing renal impairment. Preliminary data also sug gest that ABCD is an alternative to C-AmB when used empirically in pat ients with neutropenia and fever. Nevertheless, the efficacy of ABCD c ompared with that of the conventional formulation has yet to be adequa tely demonstrated and the role of ABCD relative to that of liposomal a nd other lipid-based formulations has not been determined. Conclusions : ABCD, like other lipid-based and liposomal formulations of amphoteri cin 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.