However, in the case of severe bleeding of patients on dabigatran, the antibody fragment idarucizumab reversed the anticoagulation effects of dabigatran within minutes (Pollack et al. 1991).Ī major downside of DOACs is that they don't have reversing antidotes if internal bleeding arises from their use. DuP 714 is a potent and specific thrombin inhibitor (Chiu et al. Melagatran is the active drug formed from the prodrug ximelagatran and is a competitive and rapid inhibitor of thrombin (Gustafsson et al. Because of its hepatic metabolism, it may be used in patients with renal dysfunction. It is given intravenously and is metabolised in the liver. Argatroban is a synthetic inhibitor of thrombin derived from L-arginine, which has a relatively short period of binding only to thrombin’s active site (Hursting et al. The kidneys excrete the majority (80%) of unchanged drug (Stangier et al. 2007).Ĭommercially, dabigatran is formulated as a lipophilic prodrug, dabigatran etexilate, to promote gastrointestinal absorption before it is metabolised to the active drug. They reversibly and specifically bind both clot-bound and free thrombin (unlike warfarin or heparin), as well as inhibiting thrombin-induced platelet aggregation (Wienen et al. The direct oral anticoagulant (DOAC) synthetic organic drugs dabigatran (brand name Pradaxa), argatroban (brand name Acova, Novastan Exembol in the UK) and melagatran are potent, competitive direct thrombin inhibitors (DTIs). Specifically, thrombin converts factor XI to XIa, factor VIII to VIIIa, factor V to Va, fibrinogen to fibrin, and factor XIII to XIIIa.

In the blood coagulation process, prothrombin is proteolytically cleaved to form thrombin (factor IIa) which in turn, acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin.

Pradaxa bind