Linked Life Data

14987920

Source:http://linkedlifedata.com/resource/pubmed/id/14987920

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-2-27
pubmed:abstractText
The heparin-derived oligosaccharide C3 (C3) is currently underdevelopment for the prevention and treatment of vascular dementia and senile dementia of Alzheimer's type. C3 exhibits a molecular weight of 2200-2500 Da with a narrow distribution. The objective of the present study was to assess the pharmacodynamics and pharmacokinetics of C3 in non-human primates. C3 was administered as an intravenous or subcutaneous bolus dose of 1.0 or 2.5 mg/kg. Anti-factor Xa activity, Heptest clotting time and activated partial thromboplastin time were measured to determine pharmacodynamic effects of C3 in plasma. The pharmacokinetics of C3 was primarily characterized by measuring plasma anti-factor Xa activity as a surrogate marker. The rate of absorption and elimination of C3 after administration did not change with increasing dose. The volume of distribution of C3 was small, reflecting a major distribution inside the intravascular space (110-130 ml/kg), and was independent of dose. The total clearance (16.0-21.0 ml/h/kg) and half-life (4-6 h) of C3 were also dose-independent. Within the observed dose range, a 2.5 times of the C3 dose resulted in an area under the plasma concentration-time curve that was approximately 16-27% greater than expected on the basis of linear disposition. These differences could be attributed to the endogenous release of tissue factor pathway inhibitor (TFPI) by C3 at higher doses, which is associated with the vascular effects of C3.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0049-3848
pubmed:author
pubmed:issnType
Print
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Pharmacodynamics and pharmacokinetics of C3, a heparin-derived oligosaccharide mixture, in non-human primates.
pubmed:affiliation
Department of Pharmacology and Experimental Therapeutics, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA. qma1@lumc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.