Linked Life Data

2329509

Source:http://linkedlifedata.com/resource/pubmed/id/2329509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-5-30
pubmed:abstractText
Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effects of plasma protein binding displacement on brequinar pharmacokinetics, tissue distribution, tumor distribution and antitumor efficacy were evaluated. Sodium salicylate and ibuprofen increased the percentage of free brequinar in serum in vitro, in proportion to their added concentrations. Sodium salicylate also altered the pharmacokinetics of i.v. brequinar in rats when adminstered i.v. or p.o. at 10- or 50-fold higher doses than brequinar. At the highest salicylate/brequinar dose ratio, significant increases were observed for terminal half-life, mean residence times in the body and tissues, systemic clearance, distribution clearance, the volume of the central compartment and volume of distribution at steady state. Neither salicylate nor ibuprofen increased brequinar concentrations in lung and muscle specimens from rats, 4 or 24 hr after dosing. Tumor, lung and muscle brequinar concentrations in mice were also unaffected by coadministered sodium salicylate, 4 or 24 hr after a single i.v. brequinar dose. In rats infused for 48 hr with brequinar or brequinar plus salicylate, salicylate increased the percentage of free brequinar in plasma and lungs, but total brequinar concentrations were reduced. Antitumor efficacy was evaluated by measuring the survival times of mice implanted with L1210 leukemia cells. Salicylate-treated mice had a similar brequinar dose/response profile as mice not coadministered salicylate. Ibuprofen also did not increase brequinar's antitumor potency.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
253
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-6
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Effects of plasma protein binding displacement on the pharmacokinetics, tissue and tumor concentrations and efficacy of brequinar, a highly protein-bound antitumor agent.
pubmed:affiliation
Du Pont Medical Products, Wilmington, Delaware.
pubmed:publicationType
Journal Article