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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-6-5
pubmed:abstractText
The new thrombin inhibitor CRC 220 was characterized in vivo for its antithrombotic effects. CRC 220 led to a dose-dependent prolongation of clotting parameters as determined in rats, rabbits, dogs, sheeps, pigs and monkeys. We evaluated the efficacy of CRC 220 to prevent thrombus formation in arteries and in the microcirculation in different animal models. In a rabbit model of tissue factor-induced coagulation activation, infusion of 0.5 mg/kg x h CRC 220 (3 hours) led to a significant prevention of fibrinogen decrease. In a rat model of lethal LPS-induced DIC CRC 220 significantly prevented the mortality rate after a 4h-infusion of 0.75 mg/kg x h. Thrombin-induced platelet aggregation in rat lungs could be prevented by the i.v. bolus injection of CRC 220. A dose of 0.3 mg/kg leads to a reduction of more than 80% of platelet deposition in the lung, significant inhibition was still observed 90 minutes after CRC 220 administration; at this time the inhibitor had already been cleared from plasma. Arterial thrombosis was induced in rabbits by squeezing and stenosis of the A. carotis. The i.v. bolus administration of CRC 220 dose-dependently prevented thrombus formation, an ED50 of 0.03 mg/kg was calculated. This dose was associated with only a minor prolongation of aPTT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0049-3848
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
357-68
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:7740526-Animals, pubmed-meshheading:7740526-Antithrombins, pubmed-meshheading:7740526-Blood Coagulation, pubmed-meshheading:7740526-Dipeptides, pubmed-meshheading:7740526-Disseminated Intravascular Coagulation, pubmed-meshheading:7740526-Dogs, pubmed-meshheading:7740526-Dose-Response Relationship, Drug, pubmed-meshheading:7740526-Female, pubmed-meshheading:7740526-Macaca fascicularis, pubmed-meshheading:7740526-Male, pubmed-meshheading:7740526-Mice, pubmed-meshheading:7740526-Piperidines, pubmed-meshheading:7740526-Platelet Aggregation, pubmed-meshheading:7740526-Platelet Aggregation Inhibitors, pubmed-meshheading:7740526-Rabbits, pubmed-meshheading:7740526-Rats, pubmed-meshheading:7740526-Rats, Sprague-Dawley, pubmed-meshheading:7740526-Sheep, pubmed-meshheading:7740526-Swine, pubmed-meshheading:7740526-Thrombosis
pubmed:year
1995
pubmed:articleTitle
Pharmacological characterization of a new 4-amidinophenyl-alanine thrombin-inhibitor (CRC 220).
pubmed:affiliation
Research Laboratories of Behringwerke AG, Marburg, Germany.
pubmed:publicationType
Journal Article