Liposomal and lipid-based formulations of amphotericin B.
Encapsulating amphotericin B (AmB) into liposomes or binding of AmB to other lipid carriers results in a significant reduction of toxicity of AmB and possibly an increased therapeutic index. Following promising clinical results with investigational formulations, three industrial compounds have been developed: AmBisome, Amphocil (Amphotericin B Colloidal Dispersion) and Amphotericin B Lipid Complex (ABLC, Abelcet). These three formulations differ significantly in composition and pharmacokinetics. AmB serum levels after ABLC and Amphocil administration are low, but after AmBisome much higher. However, the interpretation of the pharmacokinetic data is hampered by the inability to separate free AmB fractions from tissue-, protein- and lipid carrier bound fractions. All three compounds share a considerable reduction of nephrotoxicity. However, the acute reaction rates differ among these compounds. Amphocil showing the highest and AmBisome the lowest rate. Unfortunately, efficacy data of ongoing trials comparing these formulations with conventional AmB are scarce. Therefore, for the moment we can recommend these compounds only in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal doses of conventional AmB.
de Marie
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University Hospital Rotterdam/Dijkzigt, Dept Bacteriology, The Netherlands.
D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B