Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-2-2
pubmed:abstractText
Studies have shown that the dose-limiting toxicity of amphotericin B (AmB), a key drug for systemic mycoses, depends on its self-aggregation state. In a step toward understanding the various factors in blood mediating the toxicity of AmB, we have investigated the effect of serum albumin, the most abundant plasma protein, on the aggregation state of AmB using absorption spectroscopy. The critical aggregation concentration (CAC) of AmB, which coincides with its concentration at the onset of toxicity (hemolysis), was 1.1 microM, but rose in proportion to the level of serum albumin (1.0 to 4.0% w/v). The CAC of AmB was 8.0 microM at 4.0% w/v serum albumin, which is considerably higher than peak therapeutic levels of AmB in plasma (i.e., 2.0 microM). Serum albumin (4.0% w/v) lowered the degree of aggregation of AmB (size of aggregates) above the CAC and increased its solubility. The results suggest that serum albumin attenuates the toxicity of AmB at a membrane level by affecting its aggregation state. In this way, serum albumin in blood may balance deleterious effects of AmB mediated by serum low-density lipoproteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1589-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
The effect of serum albumin on the aggregation state and toxicity of amphotericin B.
pubmed:affiliation
School of Pharmacy, University of Wisconsin at Madison, Madison, Wisconsin 53706-1515, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.