Amphotericin B lipid complex therapy of experimental fungal infections in mice.
The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.
Clark
J M
JM
Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Whitney
R R
RR
Olsen
S J
SJ
George
R J
RJ
Swerdel
M R
MR
Kunselman
L
L
Bonner
D P
DP
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology; D004134:Dimyristoylphosphatidylcholine / Q000493:pharmacokinetics / Q000627:therapeutic use; D005079:Excipients; D005260:Female; D006660:Histoplasmosis / Q000188:drug therapy / Q000382:microbiology; D008081:Liposomes; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010715:Phosphatidylglycerols / Q000493:pharmacokinetics / Q000627:therapeutic use
D005079:Excipients; D008081:Liposomes; D010715:Phosphatidylglycerols; D000666:Amphotericin B; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine