PHARMACOKINETICS OF LIPOSOMAL AMPHOTERICIN-B (AMBISOME) VERSUS OTHER LIPID-BASED FORMULATIONS

To lower amphotericin B-associated toxicity, amphotericin B may be integrated into liposomes (AmBisome(R)) or can be administered in Intralipid(R) 20% emulsions (Ampho-B/Lipid). The present study compares the pharmacokinetic characteristics of standard amphotericin B dissolved in glucose 5% (Ampho-B/G) (n = 6) to the alternative formulations Ampho-B/Lipid (n = 8) and Ambisome (n = 10), Ampho-B/G and Ampho-B/Lipid were infused at a dose of 1 mg/kg, while the dose of AmBisome was increased to 3 mg/kg, Infusion duration was 1 h. Pharmacokinetics of Ampho-B/G, AmB/Lipid and AmBisome showed striking differences, specifically with regard to the respective Cmax and AUC values. In fact, after application of AmB/Lipid mean Cmax values were reduced to 39% and mean AUC values were lowered to 57% compared with application of Ampho-B/G in the same patients. This compares with a 1.8-fold greater Vss for Ampho-B/Lipid and a clearance rate which was 2.1-fold faster, By contrast, application of AmBisome (at a three-fold greater dose) resulted in Cmax and AUC values eight-fold and 12-fold greater than those reached by Ampho-B/G, The higher Cmax values achieved by AmBisome relate to a four-fold smaller Vss compared with Ampho-B/G. Assuming a linear relationship between AmBisome dose and Cmax, it was concluded that even at equal doses the liposomal formulation of amphotericin B would result in significantly greater Cmax and AUC values than Ampho-B/G or Ampho-B/Lipid.