Document Detail


Amphotericin B incorporated into egg lecithin-bile salt mixed micelles: molecular and cellular aspects relevant to therapeutic efficacy in experimental mycoses.
MedLine Citation:
PMID:  8192456     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cellular activities of amphotericin B (AmB) used as Fungizone were compared with those of AmB complexed to either egg lecithin and glycocholate (Egam) or egg lecithin and deoxycholate (Edam). Under conditions in which leakage of K+ from erythrocytes and cultured L cells treated with Fungizone was almost complete, Egam and Edam containing concentrations of AmB severalfold greater than the concentration of AmB in Fungizone had no effect but retained the ability to decrease the level of retention of K+ in fungal cells. Analysis by absorption and circular dichroism spectroscopy demonstrated that when these formulations containing AmB at concentrations of less than 10(-5) M were added to buffer, the AmB dissociated slowly as monomers from Egam or Edam and dissociated rapidly as a mixture of monomers and self-associated species from Fungizone. We propose that in Egam and Edam, the absence of free AmB in the self-associated form reduces the toxicity of AmB to mammalian cells, whereas the presence of monomeric AmB results in the retention of the antifungal activities of these complexes.
Authors:
J Brajtburg; S Elberg; G S Kobayashi; J Bolard
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  38     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-06-22     Completed Date:  1994-06-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  300-6     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / administration & dosage*,  pharmacokinetics*,  toxicity
Animals
Bile Acids and Salts*
Cells, Cultured
Circular Dichroism
Drug Carriers
Drug Stability
Erythrocytes / drug effects,  metabolism
Fibroblasts / drug effects,  metabolism
Humans
Lipoproteins / pharmacology
Mice
Micelles*
Mycoses / drug therapy*
Phosphatidylcholines*
Potassium / metabolism,  pharmacokinetics
Spectrophotometry
Therapeutic Equivalency
Grant Support
ID/Acronym/Agency:
AI-25903/AI/NIAID NIH HHS; AI-72640/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Drug Carriers; 0/Lipoproteins; 0/Micelles; 0/Phosphatidylcholines; 1397-89-3/Amphotericin B; 7440-09-7/Potassium
Comments/Corrections

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