Bivalirudin pharmacokinetics and molecular data

Basic chemical and pharmacological properties
Chemically it constitutes a synthetic congener of the naturally occurring drug hirudin (found in the saliva of the medicinal leech Hirudo medicinalis).

Both bivalirudin and hirudin directly inhibit thrombin by specifically binding as well to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine protease that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.

The pharmacological difference between both drugs is that Hirudin is an irreversible inhibitor of thrombin while Bivalirudin is a reversible one. This leads to a relatively small rate of severe bleedings under Bivalirudin compared to standard therapy (see below under section comparative results). When delivered by i.v.-infusion with a rate of 2.5 mg/kg/hr, the mean steady-state-concentration is 12.4 µg/ml. 80% of the drug is proteolytically cleaved, and the remaining 20% is renally metabolized. The half-life of Bivalirudin is 25 minutes.

The clinical onset of action is almost immediate after i.v.-bolus. Bivalirudin prolongs a number of coagulation parameters due to its mode of action. These are the activated clotting time (ACT), the activated partial thromboplastin time (aPPT), the thrombin time (TT), and the prothrombin time (PTT). After termination of treatment the coagulation parameters return to normal within 1 to 2 hours indicating a short action of Bivalirudin resulting in a good controllability of therapy.