Abstract
Thromboembolic disorders are the major cause of mortality and morbidity in Western societies. Coagulation enzymes, such as thrombin, factor Xa and a tissue factor/factor VIIa complex, together with platelet GPIIb/IIIa receptors, are the focal point of attention in pharmaceutical research aimed at finding new antithrombotic agents. However, finding orally active drugs for these particular molecular targets has proved to be anything but straightforward. Thrombin, factor Xa, tissue factor/factor VIIa and platelet GPIIb/IIIa receptors display a preference for molecules containing highly basic arginine and/or 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.
Keywords: Antithrombotic, prodrug, thrombin, factor Xa, factor VIIa, platelet
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