Linked Life Data

6831396

Source:http://linkedlifedata.com/resource/pubmed/id/6831396

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1983-5-5
pubmed:abstractText
The more efficacious and less cardiotoxic analogue of daunorubicin, N,N-dibenzyldaunorubicin (B2D), was found to be metabolized in rats by stepwise debenzylation that was superimposed on the known anthracycline metabolism via 13-ketone reduction and deglycosidation. Using high-pressure liquid chromatography for resolution and fluorescence for detection, we observed a series of metabolites in plasma, liver, heart, muscle, and lungs of rats receiving 10 mg B2D per kg, i.v., i.p., and p.o. Rats receiving 40 mg B2D per kg, i.v., died immediately, but this dose given p.o. was not lethal during 24 hr. Patterns of B2D and metabolites varied quantitatively with tissue and route of administration. Rat liver perfusion studies indicated extensive metabolism of B2D compared with limited metabolism of doxorubicin. These observations were consistent with an observed major first-pass effect on B2D in intact rats given B2D p.o. The predominant metabolites of B2D were the glycosidic derivatives, N-benzyldaunorubicin, daunorubicin, and their 13-dihydro derivatives. These metabolites of B2D had exhibited activity against mouse leukemia P388 as did B2D and were active in in vitro tests in which B2D was essentially inactive. These results indicate that B2D acts as a prodrug for a series of active metabolites. Conversion of B2D to these metabolites was relatively more efficient after p.o. administration than following i.v. or i.p. treatments.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1477-87
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Metabolic disposition of N,N-dibenzyldaunorubicin in the rat.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.