Ximelagatran is a prodrug that is converted to melagatran. This drug is a direct thrombin inhibitor that binds directly to the active site of thrombin, preventing coagulation and formation of blood clots due to the inactivation of the enzyme that catalyzes activation of coagulation factors V, XIII and fibrinogen. Ximelagatran is the first direct thrombin inhibitor that could be taken orally, and was thought to be a replacement for warfarin, due to not having as many dietary restrictions involved. However, it was withdrawn from testing and distribution following evidence of liver damage. After oral administration, ximelagatran is absorbed and converted to melagatran through an unknown series of reactions. From there, melagatran directly binds to thrombin, preventing its use as an enzyme. This prevents catalyzation of factor V to factor Va, which would form the prothrombinase complex and create more thrombin. It also prevents the catalysis fibrinogen or factor I to fibrin, which then polymerizes to form the blood clot. The lack of useable thrombin also prevents the catalysis of factor XIII to factor XIIIa, which is necessary to crosslink the polymerized fibrin to form a water insoluble clot.

Ximelagatran Action References