Liposome-encapsulated amphotericin B in the treatment of experimental murine candidiasis.
The efficacy of liposome-encapsulated amphotericin B in treating experimental murine candidiasis was compared with that of the commercially available amphotericin B (Fungizone). The LD50 of liposomal amphotericin B in ddY mice exceeded 10.0 mg/kg while that of Fungizone was 3.0 mg/kg. Experimental candidiasis was induced by injecting a clinical isolate of Candida albicans strain 0925-107-01, through the tail vein. With the injection of 1.7 x 10(6) colony forming units, the number of colonies in the kidneys remained between 2.1 x 10(5) and 1.2 x 10(6), whereas the number of colonies in blood, liver, spleen, lungs and heart decreased rapidly. Histological examination revealed severe pyelonephritis with fungal infiltration and a mild invasion of the heart, lungs, liver and spleen. The survival rate of mice with experimental candidiasis treated with Fungizone at a dose of 0.8 mg/kg was 50% (the maximum tolerated dose without acute lethality), whereas all mice treated with the liposomal amphotericin B at a dose of 5.0 mg/kg were alive even 42 days after the inoculation (p less than 0.01). Using liposome as a carrier for amphotericin B decreased this drug's systemic toxicity making it possible to administer doses higher than feasible with the commercial preparation and thus obtaining better therapeutic efficacy.
Miyazaki
T
T
Second Department of Internal Medicine, Nagasaki University School of Medicine.
Kohno
S
S
Kaku
M
M
Koga
H
H
Yamaguchi
K
K
D000666:Amphotericin B / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy* / Q000473:pathology; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000633:toxicity; D004337:Drug Carriers; D004361:Drug Tolerance; D005260:Female; D007928:Lethal Dose 50; D008081:Liposomes; D051379:Mice
D004337:Drug Carriers; D008081:Liposomes; D003840:Deoxycholic Acid; D000666:Amphotericin B