Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-8-3
pubmed:abstractText
Radiolabelled [3H]pentamidine is accumulated into 48-h and 7-day cultures of alveolar epithelial type 2 cells and alveolar macrophages in a linear, time and dose-dependent manner, with the rate of uptake being 15.3, 13.4 and 17.9 pmol/micrograms protein per 30 min, respectively. Uptake was not affected by metabolic inhibitors. The differential toxicity of the parent drug pentamidine, five analogues and six metabolites was assessed on freshly isolated and type 2 cells maintained in culture over 24 h. Toxicity, determined by the attachment ability of alkaline phosphatase positive cells containing lamellar bodies was greater in freshly isolated cells. Overall, three/four of the analogues proved less damaging to type 2 cells than the pentamidine with one derivative [1,3-bis(4-amidino-2-methoxy)propane], a compound particularly efficacious against pneumocystis in rats, showing minimal toxicity. Five metabolites (chain hydroxylated derivatives) were less toxic than the parent drug. However, one metabolite (N,N-dihydroxy derivative) was much more toxic than pentamidine to both type 2 cells and alveolar macrophages. It is concluded that as the type 2 cell can accumulate the drug, it represents a target cell which is particularly sensitive to pentamidine and/or some of its metabolites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
The accumulation of pentamidine and the toxic effects of the drug, its selected analogues and metabolites on isolated alveolar cells.
pubmed:affiliation
Welsh School of Pharmacy, University of Wales College of Cardiff, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't