Biodistribution of liposomal amphotericin B (AmBisome) and amphotericin B-desoxycholate (Fungizone) in uninfected immunocompetent mice and leucopenic mice infected with Candida albicans.
The biodistribution of liposomal amphotericin B (L-AmB; AmBisome) and amphotericin B-desoxycholate were compared after a single injection of drug in uninfected immunocompetent mice and in leucopenic mice 6 h after inoculation with Candida albicans. Amphotericin B-desoxycholate was administered at the maximum tolerated dose (MTD) of 0.3 mg/kg whereas L-AmB was given at either 0.3 mg/kg or the MTD of 7 mg/kg. Amphotericin B (AmB) concentrations in the blood, liver, spleen, lungs and kidneys were determined by HPLC analysis at various intervals during the 48 h after administration. The biodistribution of both preparations of AmB followed similar patterns in both uninfected immunocompetent mice as well as those that were leucopenic and infected with C. albicans. Administration of L-AmB resulted in increased concentrations of drug in the blood, liver, and spleen but decreased concentrations in the kidney and lung. Hepatosplenic uptake of L-AmB was highly dose dependent with 7 mg/kg resulting in a relatively prolonged blood circulation. Blood and tissues retained high AmB concentrations after administration of L-AmB at the MTD. By using radiolabelled L-AmB, it was found that the high AmB concentrations in blood represented liposome-associated AmB and that during circulation in blood slow release of AmB occurred.
van Etten
E W
EW
Erasmus University Rotterdam, Department of Clinical Microbiology and Antimicrobial Therapy, The Netherlands.
Otte-Lambillion
M
M
van Vianen
W
W
ten Kate
M T
MT
Bakker-Woudenberg
A J
AJ
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002177:Candidiasis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide; D004337:Drug Carriers; D005260:Female; D005710:Gallium Radioisotopes; D007553:Isotope Labeling; D007970:Leukopenia / Q000139:chemically induced / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution
D004337:Drug Carriers; D005710:Gallium Radioisotopes; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B; D003520:Cyclophosphamide