Comparing the antithrombotic efficacy of a humanized anti-factor IX(a) monoclonal antibody (SB 249417) to the low molecular weight heparin enoxaparin in a rat model of arterial thrombosis.

Abstract

A humanized inhibitory anti-factor IX(a) antibody (SB 249417) has been compared to enoxaparin (Lovenox) in a rat model of arterial thrombosis. Pretreatment of rats with either SB 249417 (3.0 mg/kg, i. v.) or enoxaparin (30.0 mg/kg, i.v. or s.c.) resulted in comparable and significant reductions in thrombus formation. However, the efficacious dose of enoxaparin resulted in >30-fold increase in the aPTT over baseline, while the efficacious dose of SB 249417 prolonged the aPTT by only approximately 3-fold. Additionally, pretreatment with SB 249417 resulted in sustained blood flow and arterial patency throughout the experiment in >80% of rats treated. In contrast, <30% of rats pretreated with enoxaparin remained patent throughout the experiment. The data in this report indicate that the selective inhibition of factor IX(a) with the monoclonal antibody SB 249417 produces a superior antithrombotic profile to that of the low molecular weight heparin enoxaparin.

• Authors: J R Toomey, M N Blackburn, B L Storer, R E Valocik, P F Koster, G Z Feuerstein
• Journal: Thrombosis research (Thromb Res) Vol. 100 Issue 1 Pg. 73-9 (Oct 01 2000) ISSN: 0049-3848 [Print] United States
• PMID: 11053619 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Enoxaparin
• Fibrinolytic Agents
• Heparin, Low-Molecular-Weight
• Factor IXa

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Blood Coagulation Tests
• Blood Flow Velocity (drug effects)
• Carotid Artery Thrombosis (chemically induced, drug therapy)
• Coronary Disease (drug therapy)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enoxaparin (pharmacology, standards, therapeutic use)
• Factor IXa (immunology)
• Fibrinolytic Agents (pharmacology, standards, therapeutic use)
• Heparin, Low-Molecular-Weight (immunology, pharmacology, therapeutic use)
• Humans
• Male
• Rats
• Rats, Sprague-Dawley
• Time Factors