Linked Life Data

12083506

Source:http://linkedlifedata.com/resource/pubmed/id/12083506

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-6-26
pubmed:abstractText
Pharmacokinetics of oligosaccharides displaying various affinities for antithrombin (AT) allowed us to show that there was a close relationship between the plasma half-life of these antithrombotic oligosaccharides and their affinity for AT. Recently, we have described new heparin mimetics comprising an AT binding domain and a thrombin binding domain separated by a neutral methylated saccharide sequence. These compounds displayed strong anti-Xa and antii-IIA activities and, in contrast to heparin, escaped neutralisation by platelet factor 4. The aim of this work was to compare the pharmacokinetics of several of these heparin mimetics in rats. These compounds differed by their length, charge and affinity for AT (AT-binding domain). The results obtained indicate that the prolongation of the AT binding domain did not modify significantly their affinities for AT. However, an increase in the number of charges leads to a decrease in the half-life. When a methylated spacer was added in order to minimise the non-specific interactions to other proteins, half-lives of the heparin mimetic were in the same range than that of the pentasaccharide used as an AT binding domain. In conclusion, this study shows the influence of the charge of the oligosaccharides on their pharmacokinetics and underlinesthe importance of minimising their non-specific binding to plasma proteins in order to obtain compounds with predictive pharmacokinetics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
985-9
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Pharmacokinetics of new synthetic heparin mimetics.
pubmed:affiliation
Sanofi-Synthélabo Recherche, Toulouse, France.
pubmed:publicationType
Journal Article