? DTIs effectively bind to, and directly inhibit the activity of circulating and clot-bound thrombin
? Thrombin plays a central role in thrombosis ? its multiple prothrombotic actions in the coagulation cascade make it a key target for therapeutic intervention in most thromboembolic diseases
? Preclinical studies in in vitro and in vivo models of thrombosis have shown dabigatran to be a potent, specific and reversible inhibitor of thrombin
? Dabigatran etexilate is a prodrug with no pharmacologic activity; once administered orally, it is rapidly absorbed and subsequently converted to the active drug dabigatran by plasma enzymes
? After oral administration of dabigatran etexilate, the plasma concentration of dabigatran reaches peak levels within 0.5?2.0 hours. Dabigatran has generally a linear pharmacokinetic profile, which means that its plasma concentration increases as the administered dose is increased. The half-life is 14?17 hours in healthy adults, which means that some anticoagulant activity remains 24 hours after administration of the last dose
? There is a good correlation between prolongation of blood coagulation assays and dabigatran plasma concentrations ? as the plasma concentration of dabigatran increases so do the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT) and international normalised ratio (INR) values
? The anticoagulant effects of dabigatran decline in parallel with its declining plasma concentration.
? Dabigatran is eliminated from the body mainly by the kidneys (up to 80%)
? Dabigatran has a favourable safety profile ? the major side effect is increased bleeding events with higher doses, which is consistent with its known pharmacologic activity
? Given that dabigatran does not undergo hepatic metabolism, there is low potential for drug?drug interactions and no potential for drug?food interactions
? In summary, dabigatran etexilate is a convenient, fixed oral dose anticoagulant, which has a rapid onset of action, provides predictable and consistent anticoagulant effects without the need for coagulation monitoring and has low potential for drug?drug interactions and no potential for drug?food interactions
Mungall D. Curr Opin Investig Drugs 2002; 3: 905?7.
Stangier J, et al. J Clin Pharmacol 2005; 45: 555¬?63.