THE USE OF LIPID FORMULATIONS OF AMPHOTERICIN-B FOR SYSTEMIC FUNGAL-INFECTIONS

Despite its considerable toxicity, amphotericin B (AmB) remains the 'g olden standard' in the treatment of many systemic fungal infections. T o reduce this toxicity, with the aim of increasing its therapeutic ind ex, AmB can be encapsulated into liposomes or bound to lipid carriers. Following promising clinical results with investigational formulation s, three industrial compounds are available at this moment: Abelcet (A mphotericin B Lipid Complex, ABLC), Amphocil (Amphotericin B Colloidal Dispersion) and AmBisome. These three formulations differ significant ly in composition and pharmacokinetics, Aii three compounds share a co nsiderable reduction of nephrotoxicity, but the number of acute reacti ons differ among these compounds, Amphocil showing the highest and AmB isome the lowest rate. Increased therapeutic indexes for all three for mulations were shown only in some of the animal models for several fun gal infections. Four recent clinical trials comparing these formulatio ns with AmB demonstrated their clinical efficacy but failed to clearly show an increased therapeutic index. Therefore these compounds can be recommended in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should probably be avoided in the initial treatment of fulminant fungal infections, since efficacy may he inferior to equal dosages of conventional AmB.