AMBISOME (LIPOSOMAL AMPHOTERICIN-B) - A COMPARATIVE REVIEW

AmBisome (NeXstar Pharmaceuticals, San Dimas, CA) is a unilamellar lip osomal formulation of amphotericin B that was recently approved for us e as empirical treatment for presumed fungal infections in febrile neu tropenic patients and for aspergillosis, candidiasis, and cryptococcos is infections refractory to amphotericin B. It is a small closed micro scopic sphere (<100 nm in diameter) with an inner aqueous core (i.e., a true liposome). AmBisome remains at an intact sphere in vitro and fo r prolonged periods of time in vivo during the processes of systemic t ransport and pharmacologic action. As a consequence of its size and in vivo stability, AmBisome has physiochemical properties and a pharmaco kinetic profile that ar e considerably different from those of current ly available lipid-complexed amphotericin B formulations, with greatly increased area under the plasma concentration-time curve and much low er clearance at equivalent doses. AmBisome liposomes can be seen to ac cumulate at sites of fungal infection. Disruption of AmBisome liposome s occurs after attachment to the fungal cell wall and results in ampho tericin B binding to fungal cell membrane ergosterol with subsequent c ell lysis. AmBisome has been shown to penetrate the cell wall of bath extracellular and intracellular forms of susceptible fungi. Journal of Clinical Pharmacology, 1998;38:583-592 (C)1998 The American College o f Clinical Pharmacology.