Overview of amphotericin B colloidal dispersion (amphocil)

Abstract

Amphotericin B colloidal dispersion (ABCD) is an equimolar mixture of amphotericin B and cholesteryl sulphate with desirable preparation and stability characteristics. It allows the intravenous delivery of amphotericin B in doses up to 7 mg/kg daily. Peak serum concentrations of amphotericin B, given as ABCD, are lower, AUC0-infinity similar and half-life longer than deoxycholate amphotericin B. In vitro activity may be altered with respect to the deoxycholate preparation, some isolates being more resistant and others more susceptible. Preclinical toxicology with ABCD revealed a safety factor of five to 19-fold compared with deoxycholate amphotericin B. Animal models of coccidioidomycosis, disseminated cryptococcosis, candidiasis and invasive aspergillosis indicated a better therapeutic ratio, especially in cryptococcosis. Phase I/II studies in humans demonstrate efficacy against coccidioidomycosis, candidiasis and aspergillosis at doses from 1-7 mg/kg/day in at least 100 patients. Renal toxicity was acceptable but infusion-related side effects and anaemia were common. Side effects appear to decrease on therapy. Comparative studies with deoxycholate amphotericin B are needed.