[Dabigatran: clinical pharmacology]
Résumé
Dabigatran (Pradaxa) is a new oral, direct, selective and reversible inhibitor of the factor IIa of the coagulation cascade. The main pharmacokinetic characteristics of dabigatran are a bioavailability of approximately 7.5%, a maximum concentration obtained in 0.5 to 2 hours, a terminal half-life of elimination of 7 to 17 hours, a renal way of elimination, 80% as unchanged form and 20% as glucuronide conjugate. The main sources of variability are the renal function, the gastric motility, especially during the early post-operative period and a potential interaction with amiodarone. This compound can be orally administrated, once or twice daily, without any biological monitoring and without any need for dose adjustment. There is a contra-indication in case of severe renal or liver insufficiency. Two phases II with 2287 patients were carried out to for venous thromboembolic (VTE) prophylaxis after major orthopaedic surgery, showing that 150 mg and 220 mg once daily could be the optimal dose regimen to assess in phase III. One phase II with 502 patients vas carried out for the prevention of thromboembolic complications of atrial fibrillation (AF) showing that 110 mg or 150 mg twice daily could be the optimal dose regimen to evaluate in the following phases 3. From this study in AF patients, a dose regimen of 150 mg bid has been chosen to be evaluated for the treatment of VTE. No strong signal for a potential liver toxicity was shown during these studies.