Amphotericin B (AMB): It is obtained from Streptomyces nodosus. Chemistry and mechanism of action The polyenes possess a macrocyclic ring, one side of which has several conjugated double bonds and is highly lipophilic, while the other side is hydrophilic with many OH groups. A polaraminosugar and a carboxylic acid group are present at one end in some. They are all insoluble in water and unstable in aqueous medium. The polyenes have high affinity for ergosterol present in fungal cell membrane: combine with it, get inseed into the membrane and several polyene molecules together orient themselves in such a way as to form a &;micropore&;. The hydrophilic side forms the interior of the pore through which ions, amino acids and other watersoluble substances move out. The micropore is stabilized by membrane sterols which fill up the spaces between the AMB molecules on the lipophilic side-constituting the outer surface of the pore. Thus, cell permeability is markedly increased. New amphotericin B formulations In an attempt to improve tolerability of i.v. infusion of AMB, reduce its toxicity and achieve targeted delivery, 3 new lipid formulations of AMB have been produced. (a) Amphotericin B lipid complex (ABLC): Contains 35% AMB incorporated in ribbon like paicles of dimyristoyl phospholipids. ( b ) Amphotericin B colloidal dispersion (ABCO). Disc shaped paicles containing 50% each of AMB and cholesteryl sulfate are prepared as aqueous dispersion (c) Lpi osomal amphotericin B (small unilamellar vesicles SUV): Consists of 10% AMB incorporated in uniform sized (60-80 nM) unilamellar liposomes made up of lecithin and other biodegradable phospholipids. The special features of these preparations are: * They, except ABCD, produce milder acute reaction (especially liposomal formulation) on i.v. infusion. * They can be used in patients not tolerating infusion oi conventional AMB formulation. * They have lower nephrotoxicity. * They cause minimal anaemia. * The liposomal preparation delivers AMB paicularh* to reticuloendothelial cells in liver and spleen-----especialh valuable for kala azar and in immunocompromised patients. However, some preparations, especially ABLC and ABCD, produce lower AMB levels and their clinical efficacy relative to conventional formulations appear to be lower. Though none of the above formulations is more effectivein deep mycosis than conventional AMB, the liposomal AMB reduces equivalent blood levels, has similar clinical efficacy with less acute reaction and renal toxicity. It thus apears more satisfactory. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:757,758,759