Linked Life Data

9806363

Source:http://linkedlifedata.com/resource/pubmed/id/9806363

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-1-6
pubmed:abstractText
This article describes the equivalent antiplatelet/antithrombotic effects of DMP755 at comparable doses by intranasal and i.v. administration but required substantially higher doses with the oral administration route. Antiplatelet and antithrombotic efficacy of DMP755 or its free acid form XV459 were determined in dogs. Arterial thrombosis models were induced either electrolytically (200 microA anodal current) in the carotid artery or mechanically by external clamping of femoral artery along with stenosis, which result in either total occlusive thrombus formation or cyclic flow reduction (CFR), respectively. Either DMP755 or its free acid form, XV459 demonstrated maximal and comparable antiplatelet efficacy at 0.025-0.1 mg/kg, intravenous (i.v.) or intranasal but not oral (PO) in mongrel dogs. The antiplatelet efficacy of DMP755 at 0.1 mg/kg, intranasal, or i.v. was determined in a cross-over design (n=8 in each group). In this study, a comparable and maximal antiplatelet efficacy for DMP755 after intranasal or i.v. was demonstrated suggesting 100% intranasal bioavailability as compared with the modest antiplatelet efficacy at 0.1 mg/kg, p.o. DMP755 administered at 0.1 mg/kg, intranasally or i.v. or at 0.3 mg/kg, p.o. prevented the incidence of electrolytic injury-induced arterial thrombosis in the carotid artery thrombosis model and prevented the incidence of cyclic flow reduction in mechanically injured and stenosed femoral artery. In conclusion, DMP755 has a comparable intranasal and intravenous antiplatelet/antithrombotic profiles along with a significant improvement over its oral profiles. These data also suggest the potential utility of intranasal DMP755 in various acute and chronic thromboembolic disorders. This is the first report of intranasal bioavailability of a glycoprotein receptor antagonist.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0049-3848
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-24
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Intranasal antiplatelet/antithrombotic efficacy of a novel platelet GPIIB/IIIA receptor antagonist DMP755.
pubmed:affiliation
DuPont Pharmaceuticals Company, Wilmington, Delaware 19880-0400, USA. shaker.a.mousa@dupontpharma.com
pubmed:publicationType
Journal Article