Treatment of murine candidiasis and cryptococcosis with amphotericin B incorporated into egg lecithin-bile salt mixed micelles.
Amphotericin B (AmB) with deoxycholate (Fungizone) and AmB incorporated into mixed micelles (AmB-mixMs) composed of egg lecithin with glycocholate, deoxycholate, or taurocholate were compared as treatments for murine infections. For mice infected with Candida albicans, treatment consisted of a single intravenous injection; for mice infected with Cryptococcus neoformans, treatment consisted of two intravenous injections. The maximal tolerated doses of AmB as Fungizone were 1.25 mg/kg of body weight in mice with candidiasis and 2.5 mg/kg of body weight in mice with cryptococcosis. The AmB-mixMs were nontoxic to mice at doses of 80 and 100 mg/kg of body weight and were therapeutically more active than the maximal tolerated dose of Fungizone in both models of infection. However, when Fungizone or AmB-mixMs were administered at equivalent doses of AmB, AmB-mixMs were more active in treating murine candidiasis, whereas Fungizone was more active in treating murine cryptococcosis.
Brajtburg
J
J
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Elberg
S
S
Travis
S J
SJ
Kobayashi
G S
GS
D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001647:Bile Acids and Salts; D002177:Candidiasis / Q000188:drug therapy*; D003453:Cryptococcosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008823:Micelles; D010713:Phosphatidylcholines
D001647:Bile Acids and Salts; D004337:Drug Carriers; D008823:Micelles; D010713:Phosphatidylcholines; D000666:Amphotericin B