Oral platelet glycoprotein IIb/IIIa receptor inhibitors--Part I.

With the central importance of antiplatelet therapy in patients with coronary artery disease and the numerous positive trials with glycoprotein (GP) IIb/IIa inhibitors given intravenously, it was hoped that one could extend the benefit of IIb/IIIa inhibition to long-term treatment. Although the hypothesis that prolonged oral IIb/IIIa inhibition was appealing, many issues have been identified in the initial Phase II trials that would limit the usefulness of these compounds. Variability of the level of platelet inhibition was one major culprit that distinguished the oral compounds from intravenous ones. The problems that arose were that increased bleeding has been seen when levels of platelet inhibition are high (e.g., > 90%) and that, conversely, efficacy would likely be limited when levels of platelet inhibition were low. If further development of this class of drugs is undertaken, formal dosing studies would have to establish an oral dosing strategy that achieves appropriately high (80-95% inhibition) and steady levels of inhibition.