Thromboembolic disorders are the major cause of mortality and morbidity in Western societies. Coagulation enzymes, such as thrombin, factor Xa and a tissue factoržfactor VIIa complex, together with ...platelet GPIIbžIIIa receptors, are the focal point of attention in pharmaceutical research aimed at finding new antithrombotic agents. However, finding orally active drugs forthese particular molecular targets has proved to be anything but straightforward. Thrombin, factor Xa, tissue factoržfactor VIIa and platelet GPIIbžIIIa receptors display a preference for molecules containing highly basic arginine andžor acidic aspartate moieties, which are, however, associated with poor bioavailability after oral application. Different approaches have been taken to achieve favourable absorption, metabolism, distribution and clearance, without compromising the antithrombotic activity of the compounds. This review highlights the use of the prodrug principle in optimising antithrombotic agents.
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