Linked Life Data

10052902

Source:http://linkedlifedata.com/resource/pubmed/id/10052902

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-8-9
pubmed:abstractText
Heat-induced 'superaggregation' of deoxycholate-amphotericin B (AmB-DOC, Fungizone) was shown previously to reduce the in-vitro toxicity of this antifungal agent. We compared AmB-DOC with the formulation obtained by heating the commercial form (Fungizone, Bristol Myers Squibb, Paris, France) for 20 min at 70 degrees C, in the treatment of murine infections. An improvement of antifungal activity was obtained with heated AmB-DOC formulations due to a lower toxicity which allowed the administration of higher drug doses than those achievable with the commercial preparation. Single intravenous injections of heated AmB-DOC solutions were demonstrated to be two-fold less toxic than unheated ones to healthy mice. For mice infected with Candida albicans, the maximum tolerated dose was higher with heated than with unheated AmB-DOC solutions. In the model of murine candidiasis, following a single dose of heated AmB-DOC 0.5 mg/kg, 85% of mice survived for 3 weeks, whereas at this dose the immediate toxicity of the standard formulation in infected mice restricted the therapeutic efficacy to 25% survival. Both formulations were equally effective in increasing the survival time for murine cryptococcal pneumonia and meningoencephalitis. Injection of heated AmB-DOC solutions at a dose two-fold higher than the maximal tolerated dose observed with the unheated preparation (1.2 mg/kg) increased the survival time by a factor of 1.4 in cryptococcal meningoencephalitis. These results indicate that mild heat treatment of AmB-DOC solutions could provide a simple and economical method to improve the therapeutic index of this antifungal agent by reducing its toxicity on mammalian cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0305-7453
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
779-85
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
In-vivo therapeutic efficacy in experimental murine mycoses of a new formulation of deoxycholate-amphotericin B obtained by mild heating.
pubmed:affiliation
Laboratoire de Physicochimie Biomoléculaire et Cellulaire, CNRS UA 2056, Université P. et M. Curie, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't