Effects of Intravenous Enoxaparin and Intravenous Inogatran in an Electrolytic Injury Model of Venous Thrombosis in the Dog.
The objective of this study was to compare the effectiveness of the low molecular weight heparin, enoxaparin (Lovenox((R))), and inogatran (a direct thrombin inhibitor) in a canine electrolytic injury model of venous thrombosis. Effectiveness was defined as the ability of either drug to prolong the following parameters: activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), and time to formation of an occlusive thrombus in the vein. There were 5 dogs and 10 vessels for each group (the right and left femoral veins were used in each dog to measure time to occlusion). Dogs were randomly assigned to one of six groups: (1) saline controls; (2) low-dose inogatran (0.075 mg/kg IV bolus followed by a 5 µg/kg/min infusion); (3) mid-dose inogatran (0.25 mg/kg IV bolus followed by a 20 µg/kg/min infusion); (4) high-dose inogatran (0.75 mg/kg IV bolus followed by a 50 µg/kg/min infusion); (5) low-dose enoxaparin (100 units/kg IV bolus followed by a 50 U/kg/h infusion); and (6) high-dose enoxaparin (200 U/kg IV bolus followed by a 100 U/kg/h infusion). Administration of inogatran resulted in dose-dependent increases in aPTT, TT, and PT, and administration of enoxaparin resulted in dose-dependent increases in aPTT and TT. There were no changes in hemodynamics. The time to occlusion in the control group averaged 81.7 +/- 9.9 minutes compared with 141.8 +/- 12.7, 185.8 +/- 17.6, and 226.9 +/- 8.8 minutes with the low, mid, and high doses of inogatran, and 131 +/- 20.3, and 183.0 +/- 19.0 minutes with the low and high doses of enoxaparin. Bleeding times were elevated by inogatran and enoxaparin, but no appreciable differences were detected between the two compounds. In summary, the direct thrombin inhibitor inogatran, administered intravenously, was as effective as the low molecular weight heparin enoxaparin in a canine model of venous thrombosis induced by electrolytic injury, supporting the conclusion that direct antithrombins may prove useful for prevention and treatment of deep venous thrombosis.
Ignasiak
DP
Vascular and Cardiac Diseases Section, and Biometrics Section, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, Michigan, USA.
McClanahan
TB
Bousley
RE
Juneau
PL
Gallagher
KP