Lipid Formulations for Amphotericin B: Does the Emperor Need New Clothes?

For many years, the polyene amphotericin B deoxycholate (AMBd) has been the emperor of systemic antifungal therapy. Unfortunately, the great efficacy of amphotericin B has been matched by substantial toxicity. Efforts to develop less toxic alternatives to AMBd have focused on repackaging amphotericin B in new clothes, that is, lipid vehicles. These vehicles have been designed to target sites of fungal infection but spare the kidneys [1-5]. In general, lipid-associated amphotericin B preparations achieve lower renal concentrations than does AMBd, and they are concentrated in reticuloendothelial tissues such as the liver and spleen. Pharmacokinetics variables, including tissue distribution and clearance, vary with the size, charge, amount, and type of lipid in the preparations.

The lipids have been developed in four major forms [4]. The first is amphotericin B in true liposomes (AMB1); liposomes are microspheres composed of lipid membranes surrounding an aqueous central core. Amphotericin B is located in the membrane, at a relatively low 10% concentration. The second form is amphotericin B lipid complex (ABLC), which includes an approximately 33% concentration of amphotericin B in microparticulate polymorphic sheets and ribbons. The third form is amphotericin B colloidal dispersion (ABCD), in which amphotericin B is intercalated in a 1:1 ratio with cholesteryl sulfate in disc-like particles. All three preparations have been evaluated in open clinical studies, usually at dosages of 1, 3, or 5 mg/kg of body weight per day. Even at higher dosages, these preparations are consistently less nephrotoxic than AMBd at 1 mg/kg per day [1, 2, 4, 6, 7].

Most of our current knowledge derives from open clinical trials; many patients have been …