Bivalirudin (BG-8967) is a reversible inhibitor of α- and ζ-thrombin (Kis = 2.56 and 1.84 nM, respectively), enzymes that exhibit high fibrinogen-clotting activities.

α-thrombin:2.56 nM (Ki, cell free)

Whereas 0.1 microM-hirudin and 0.1 microM-Bivalirudin (i.e. less than 10% of the concentration of prothrombin in plasma) inhibited Factor X, Factor V, and prothrombin activation. Concentrations of hirudin and hirulog-1 equimolar to and 5 times greater than those of alpha-thrombin respectively abrogated Factor V activation by exogenous alpha-thrombin [2].

Deposition in aspirin-treated groups receiving low-, medium-, and high-dose Bivalirudin decreased in a dose-dependent manner by 37%, 44%, and 56%, respectively. As the dose of Bivalirudin was increased, the plasma Bivalirudin levels and activated partial thromboplastin time ratios (final: initial) also increased in a dose-dependent manner. The mean plasma Bivalirudin levels ranged from 0.74 micrograms/ml in the low-dose Bivalirudin group to 2.55 micrograms/ml in the high-dose Bivalirudin group, and the corresponding activated partial thromboplastin time ratios were 1.5 and 3.3 [3].

Animals were randomly assigned to one of five groups: control (no aspirin or hirulog); aspirin alone (10 mg/kg); aspirin plus low-dose hirulog (0.2 mg/kg bolus followed by 0.5 mg/kg/hr); aspirin plus medium-dose hirulog (0.4 mg/kg bolus followed by 1.0 mg/kg/hr); or aspirin plus high-dose hirulog (0.6 mg/kg bolus followed by 1.5 mg/kg/hr). Hirulog was infused before surgery and continued until termination of the experiment 30 minutes after endarterectomy [3].