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
Current Pharmaceutical Design
Title: Metabolism-Directed Optimisation of Antithrombotics: The Prodrug Principle
Volume: 12 Issue: 1
Author(s): L. Peterlin-Masic, J. Cesar and A. Zega
Affiliation:
Keywords: Antithrombotic, prodrug, thrombin, factor Xa, factor VIIa, platelet
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.
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Cite this article as:
Peterlin-Masic L., Cesar J. and Zega A., Metabolism-Directed Optimisation of Antithrombotics: The Prodrug Principle, Current Pharmaceutical Design 2006; 12 (1) . https://dx.doi.org/10.2174/138161206775193172
DOI https://dx.doi.org/10.2174/138161206775193172 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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