Ximelagatran is dosed twice daily (7). In patients with chronic nonvalvular atrial fibrillation, oral ximelagatran 36 mg twice daily has been shown to be effective. For VTE prophylaxis, two approaches to dosing ximelagatran have been used: monotherapy and combination therapy. A daily dose of 24 mg and 36 mg has been studied in patients undergoing knee arthroplasty. The first dose is given on the morning after surgery or at least 12 hours after surgery, and treatment is continued for 7 to 12 days. In patients undergoing total knee or hip replacement surgery, the most effective therapy has been a single dose of subcutaneous melagatran 2 mg just before surgery (knife-to-skin) followed by melagatran 3 mg subcutaneously after surgery and then oral ximelagatran 24 mg twice daily for a total treatment duration of 8 to 11 days.

The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model.