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Prodrugs pp 1395-1402 | Cite as

Case Study: Ximelagatran: A Double Prodrug of Melagatran

  • Olafur S. Gudmundsson
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)

Abstract

Ximelagatran was designed to increase the bioavailability of melagatran, a potent thrombin inhibitor, by eliminating charges and thus increasing the lipophilicity of the molecule. Melagatran, like most other thrombin inhibitors, contains a strongly basic benzamidine group with a pKa of 11.5 that is protonated at the pH of the intestinal tract and hinders intestinal absorption. Furthermore, melagatran also contains an acidic carboxylic group with a pKa of 2.0, which is ionized at physiological pH. Melagatran also contains a secondary amine with a pKa of 7.0. The effect of the charges on the oral absorption of melagatran was observed when the compound was initially dosed orally and a low and variable bioavailability of 3–7% was observed (Gustafsson et al., 2001).

Keywords

Nitric Oxide Ethyl Ester Secondary Amine Oral Absorption Direct Thrombin Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Olafur S. Gudmundsson
    • 1
  1. 1.Discovery PharmaceuticsBristol Myers Squibb Co.Princeton

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