Direct thrombin inhibitors are not equally effective in vivo against arterial thrombosis in vivo evaluation of DuP714 and Argatroban in a porcine angioplasty model and comparison to r-hirudin

Qualitative differences in antithrombotic efficacy between thrombin inhibitors may be explained by the affinity for which they bind thrombin. This affinity is inversely proportional to the inhibitory constant for the agent (Ki). Thrombin inhibitors, DuP714 (Ki=10(-11)) and argatroban (Ki=10(-8)), we...

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Bibliographic Details
Published in:Thrombosis research 2005, Vol.116 (6), p.525-532
Main Authors: MCBANE, Robert D, HASSINGER, Nancy L, MRUK, Jozef S, GRILL, Diane E, CHESEBRO, James H
Format: Article
Language:English
Subjects:
Angioplasty, Balloon
Animals
Anticoagulants - administration & dosage
Biological and medical sciences
Blood and lymphatic vessels
Blood. Blood coagulation. Reticuloendothelial system
Boron Compounds - pharmacology
Cardiology. Vascular system
Diseases of the cardiovascular system
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Drug Evaluation, Preclinical
Hirudins - administration & dosage
Medical sciences
Oligopeptides - pharmacology
Pharmacology. Drug treatments
Pipecolic Acids - administration & dosage
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Recombinant Proteins - administration & dosage
Swine
Thrombin - antagonists & inhibitors
Thrombosis - drug therapy
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Summary:Qualitative differences in antithrombotic efficacy between thrombin inhibitors may be explained by the affinity for which they bind thrombin. This affinity is inversely proportional to the inhibitory constant for the agent (Ki). Thrombin inhibitors, DuP714 (Ki=10(-11)) and argatroban (Ki=10(-8)), were compared to our previous studies with r-hirudin (Ki=10(-13)). Prior to balloon angioplasty, thirty pigs randomly received DuP714 (0.1 mg/kg bolus and 0.6 mg/kg/h infusion; n=8), argatroban (0.2 mg/kg/min. continuous infusion; n=9), or saline (n=17). Injured arterial segments were measured for (111)In-platelet and 125I-fibrin(ogen) deposition and the incidence of macroscopic thrombus. In DuP714-treated animals, platelet and fibrin(ogen) deposition were significantly lower than controls in both carotid (10+/-2 vs. 62+/-18 and 20+/-4 vs. 74+/-6) and coronary (10+/-4 vs. 160+/-63 and 17+/-3 vs. 86+/-22) arteries (p
ISSN:0049-3848
1879-2472
DOI:10.1016/j.thromres.2005.02.010