Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-5-14
pubmed:abstractText
1. UK-240,455 ((+) 6,7-dichloro-5-[N-(2-hydroxyethyl)methanesulphonamido]-2,3 (1H,4H)-quinoxalinedione) is a potent, selective N-methyl D-aspartate (NMDA) glycine site antagonist that is being evaluated for the potential treatment of stroke. 2. UK-240,455 is predominately excreted unchanged in urine (58-68%) in rats, dogs and man following intravenous administration. The remainder of the dose is excreted unchanged in the faeces. It is considered that UK-240,455 is predominantly cleared by active renal tubular secretion and active hepatobiliary transport. In man, there is evidence that UK-240,455 undergoes glucuronidation. However, there is no evidence for this in rats and dogs. 3. UK-240,455 has a short elimination half-life in rats, dogs and man (0.4-1.4 h) and clearances of 12, 13 and 6 ml min(-1) kg(-1), respectively. The compound shows limited tissue distribution with volumes of distribution of 0.4-0.8 l kg(-1) in rats, dogs and man. The species' variation in pharmacokinetic parameters was related allometrically when plasma protein binding was taken in to account. Hence, active hepatic or renal clearance processes for this compound were conserved across species. 4. Cerebrospinal fluid and brain concentrations of UK-240,455 were determined in rats. The cerebrospinal fluid/plasma concentration ratio of UK-240,455 was 4.3%, which was similar to the plasma-free fraction of this compound (3%), indicating good blood-brain barrier permeability. Brain tissue concentrations were low (0.7% of the total plasma concentrations).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
541-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12746109-Adolescent, pubmed-meshheading:12746109-Adult, pubmed-meshheading:12746109-Animals, pubmed-meshheading:12746109-Bile, pubmed-meshheading:12746109-Binding Sites, pubmed-meshheading:12746109-Blood Proteins, pubmed-meshheading:12746109-Caco-2 Cells, pubmed-meshheading:12746109-Cell Membrane Permeability, pubmed-meshheading:12746109-Central Nervous System, pubmed-meshheading:12746109-Dogs, pubmed-meshheading:12746109-Glycine, pubmed-meshheading:12746109-Humans, pubmed-meshheading:12746109-Male, pubmed-meshheading:12746109-Middle Aged, pubmed-meshheading:12746109-N-Methylaspartate, pubmed-meshheading:12746109-Quinoxalines, pubmed-meshheading:12746109-Rats, pubmed-meshheading:12746109-Rats, Sprague-Dawley, pubmed-meshheading:12746109-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:12746109-Tissue Distribution
pubmed:year
2003
pubmed:articleTitle
Pharmacokinetics and disposition of a novel NMDA glycine site antagonist (UK-240,455) in rats, dogs and man.
pubmed:affiliation
Department of Drug Metabolism, Pfizer Global Research and Development, Sandwich CT13 9NJ, UK. rob_webster@sandwich.pfizer.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't