Development of glycoprotein IIb–IIIa antagonists: translation of pharmacodynamic effects into clinical benefit

Abstract

This article will review the development of glycoprotein IIb–IIIa antagonists, with particular emphasis on the characteristics and pharmacodynamic studies of each agent that is available for clinical use. Abciximab is a Fab fragment of the 7E3 antibody that has high affinity and a slow rate of dissociation from glycoprotein IIb–IIIa. In contrast, the small molecules eptifibatide and tirofiban, have a much more rapid rate of dissociation, with an off time of 10 to 15 s. Accordingly, the circulating pool of abciximab is predominantly associated with platelets, whereas maintenance of a consistent concentration of tirofiban and eptifibatide in the blood is critical in order to achieve and sustain their inhibitory effects. The affinity of abciximab and tirofiban for glycoprotein IIb–IIIa are substantially greater than that of eptifibatide, necessitating maintenance of greater molar concentrations of eptifibatide in blood in order to achieve effective inhibition of the binding of fibrinogen to the activated conformer of glycoprotein IIb–IIIa.

• antiplatelet
• glycoprotein IIb–IIIa
• kinetics
• pharmacodynamics
• platelet