Dabigatran/Dabigatran etexilate

Because of the crucial role of thrombin in the coagulation cascade and platelet activation, the enzyme is a primary target for the development of anticoagulant and antithrombotic drugs. The peptidomimetic dabigatran and its oral double prodrug dabigatran etexilate are univalent direct thrombin inhibitors. Pharmacological studies indicate that dabigatran potently interferes with the coagulation cascade, being highly selective for thrombin over most other serine proteases. Dabigatran and dabigatran etexilate have proven to be well tolerated in vivo in animal models. Pharmacokinetic studies indicate that thrombin activity is dose-dependently inhibited following administration of the prodrug. Pharmacokinetic and pharmacodynamic parameters increase proportionally with dose. Food delays but does not affect the extent of absorption of the agent. Clinical studies indicated good safety. Higher plasma levels of dabigatran were associated with a lower incidence of deep venous thrombosis (DVT). Moreover, dabigatran etexilate at the doses examined has proven to be safe and effective in the treatment of venous thromboembolism (VTE) compared with other anticoagulants such as warfarin.