Mechanism of Action
Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. Abciximab also binds to the vitronectin receptor (αvβ3) found on platelets and endothelial cells.
Abciximab is the Fab fragment of the chimeric monoclonal antibody 7E3. It is directed against the glycoprotein (GP) IIb/IIIa (αIIbβ3) receptor located on the surface of human platelets.
The vitronectin receptor mediates the pro-coagulant properties of platelets and proliferative properties of vessel wall endothelial and smooth muscle cells. Because of its dual specificity, abciximab more effectively blocks the burst of thrombin generation that follows platelet activation than agents which inhibit GPIIb/IIIa alone.
Distribution / Elimination
Following intravenous bolus administration of abciximab, free plasma concentrations decrease very rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. Platelet function generally recovers over the course of 48 hours, although abciximab remains in the circulation for 15 days or more in a platelet-bound state. Intravenous administration of a 0.25 mg/kg bolus dose of abciximab followed by continuous infusion of 10 µg/min (or a weight adjusted infusion of 0.125 µg/kg/min to a maximum of 10 µg/min) produces relatively constant free plasma concentrations throughout the infusion. At the termination of the infusion period, free plasma concentrations fall rapidly for approximately 6 hours then decline at a slower rate.
Preclinical Safety Data
Available non-clinical data reveal no special hazard for humans.