Lipid formulations of amphotericin B: recent progress and future directions

Abstract

Three lipid formulations of amphotericin B are now either marketed for clinical use or undergoing further study before they can be approved in various countries worldwide. Amphotericin B lipid complex (ABLC; Abelcet, Liposome Company, Princeton, NJ) is a concentration of ribbonlike structures of a bilayered membrane formed by combining a 7:3 molar ratio of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with amphotericin B. Amphotericin B colloidal dispersion (ABCD; Amphocii, Sequus Pharmaceuticals, Menlo Park, CA) is composed of disklike structures of cholesteryl sulfate complexed with amphotericin B. AmBisome (Nexstar, San Dimas, CA), the only true liposomal amphotericin B, consists of small unilamellar vesicles made up of a bilayer membrane of hydrogenated soy phosphatidylcholine and distearoylphosphatidylglycerol stabilized with cholesterol in a 2:0.8:1 ratio combined with amphotericin B. All of the preparations appear to be preferentially accumulated in organs of the reticuloendothelial system, as opposed to the kidney. In vivo animal models as well as current clinical experience suggest that use of these formulations results in overall improvement in the therapeutic index. Patients with life-threatening mycosis for whom therapy has failed or who are intolerant to therapy with amphotericin B deoxycholate have been successfully treated with these formulations. However, further study is warranted to help clarify the usefulness of each of the lipid formulations as first-line therapy for documented or suspected invasive fungal infections.