Amphotericin B (Fungilin, Fungizone, Abelcet, AmBisome, Fungisome, Amphocil, Amphotec) is a polyene antifungal drug, often used intravenously for systemic fungal infections. It was originally extracted from Streptomyces nodosus, a filamentous bacterium, in 1955 at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the Orinoco River region of Venezuela. Its name originates from the chemical's amphoteric properties. Two amphotericins, Amphotericin A and Amphotericin B are known, but only B is used clinically because it is significantly more active in vivo. Currently the drug is available as plain Amphotericin B, as cholesteryl sulfate complex, as lipid complex, and as liposomal formulation. The latter formulations have been developed to improve tolerability for the patient but may show considerably different pharmacokinetic characteristics compared to plain Amphotericin B.
Amphotericin B is believed to interact with membrane sterols (ergosterol) to produce an aggregate that forms a transmembrane channel. Intermolecular hydrogen bonding interactions among hydroxyl, carboxyl and amino groups stabilize the channel in its open form, destroying activity and allowing the cytoplasmic contents to leak out.
Intravenously administered Amphotericin B has also been associated with multiple organ damage in therapeutic doses. Nephrotoxicity (kidney damage) is a frequently reported side-effect, and can be severe and/or irreversible. It is much milder when delivered via liposomes (AmBisome) if possible. Electrolyte imbalances (e.g. hypokalemia and hypocalcemia) may also result. In the liver, increased liver enzymes and hepatotoxicity (up to and including fulminant liver failure) are common. In the circulatory system, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmias (including ventricular fibrillation), and even frank cardiac failure have been reported. Skin reactions, including serious forms, are also possible.
AmBisome is a liposomal formulation of amphotericin B for injection, developed by NeXstar Pharmaceuticals (acquired by Gilead Sciences in 1999). It is marketed by Gilead in Europe and licensed to Astellas Pharma (formerly Fujisawa Pharmaceuticals) for marketing in the USA, and Sumitomo Pharmaceuticals in Japan.
Fungisome is a liposomal complex of Amphotericin B and being the latest and cheapest addition to the lipid formulations of Amphotericin B has many advantages. It is marketed by Lifecare Innovations of India. Other formulations include Amphotec (Intermune) and Abelcet (Enzon Pharmaceuticals).
Abelcet is not a liposomal preparation but rather a lipid complex preparation.
Liposomal Amphotericin B: A Review of its Use as Empirical Therapy in Febrile Neutropenia and in the Treatment of Invasive Fungal Infections
Feb 01, 2009; Summary Abstract Liposomal amphotericin B (AmBisome®) is a lipid-associated formulation of the broad-spectrum polyene antifungal...
A drug use evaluation of amphotericin B lipid complex injection following institution of new treatment guidelines at a tertiary teaching medical center
Sep 01, 2006; Abstract A drug use evaluation at Wake Forest University Baptist Medical Center (WFUBMC) was initiated following a change in...