Comparison of the Physicochemical, Antifungal, and Toxic Properties of Two Liposomal Amphotericin B Products

• DOI: 10.1128/aac.00870-07
• Publication Date: 2007-10-29T23:05:32Z
• Authors: Jon A. Olson; Jill P. Adler-Moore; Gerard M. Jensen; Julie Schwartz; M. Cecilia Dignani; Richard T. Proffitt
• Keywords: Blood urea nitrogen

ABSTRACT Small unilamellar amphotericin B liposomes can reduce the toxicity of B. In this study, we compared physical, antifungal, pharmocokinetic, and toxic properties two liposomal products, AmBisome Anfogen, that have same chemical composition but are manufactured differently. vitro tests included determinations MICs concentrations causing release 50% intracellular potassium from red blood cells (K 50 values) to assess toxicity. The lethal dose (LD ) was evaluated by using uninfected C57BL/6 mice single intravenous (i.v.) doses 1 100 mg/kg body weight. Multiple i.v. dosing over 18 days performed with 0.5, 1.0, or 5.0 mg Anfogen/kg 5.0, 25 AmBisome/kg evaluate chronic DBA/2 were infected intranasally 2.5 × 10 6 Aspergillus fumigatus conidia, treated for 3 4 3.0, 7.5 3, 5, 7.5, 15 AmBisome/kg, drugs kidneys (by measurement urea nitrogen creatinine levels histopathology) drug efficacy. median particle size 77.8 nm 111.5 Anfogen. K values significantly lower Anfogen (0.9 μg/ml) than (20 μg/ml), LD >100 mg/kg, versus Anfogen/kg. There significant renal tubular necrosis in given no AmBisome-treated mice. at also more efficacious treatment pulmonary aspergillosis, based on survival weight loss data numbers CFU per gram lung. conclusion, efficacy these products different, thus, not comparable.