Linked Life Data

9806948

Source:http://linkedlifedata.com/resource/pubmed/id/9806948

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-12-3
pubmed:abstractText
The in vivo metabolism and excretion of zafirlukast [Accolate; 4, 5-cyclopentoxycarbonylamino-3-[(2-methoxy-4,2- methylphenylsulfonylaminocarbonyl)phenylmethyl]-1-methylindole], a selective peptide leukotriene receptor agonist, were investigated in mice, rats, and dogs. Leukotrienes are a class of compounds that have been identified as being responsible for the contraction of human airway and lung vascular smooth muscle. A chemical agent that is effective in blocking the induced constricting actions of leukotrienes could be used to treat inflammatory processes in the pulmonary system. Zafirlukast has been shown to be clinically efficacious and has been approved for the treatment of asthma in humans. To determine the metabolic fate of zafirlukast, the radiolabeled compound was administered orally to mice, rats, and dogs and iv to rats and dogs. Plasma, urine, and feces samples were collected, assayed for radioactivity, and profiled for metabolites. Nearly all of the [14C]zafirlukast-derived radioactivity was excreted in the feces of the test species, indicating biliary clearance as the major route of elimination from the systemic circulation. The primary routes of metabolism in all species studied involved hydrolysis of the amide linkage at the 5-aminoindole position and hydroxylation at one or more sites. Additional metabolites were formed by N-acetylation (not in dogs), demethylation of the indole nitrogen, and N-desmethylation. Accolate is a registered trademark, property of Zeneca Ltd.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1069-76
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Metabolism and excretion of zafirlukast in dogs, rats, and mice.
pubmed:affiliation
Drug Disposition and Metabolism Department, Zeneca Pharmaceuticals Group, Wilmington, DE 19897, USA. ron.savidge@phwilm.zeneca.com
pubmed:publicationType
Journal Article