Edoxabán. Propiedades farmacocinéticas y farmacodinámicas

Abstract

Edoxaban is a potent, selective, direct, reversible inhibitor of coagulation factor Xa. Because of its mechanism of action, edoxaban prolongs the prothrombin time and the activated partial thromboplastin time and reduces anti-factor-Xa activity. In both in vitro and in vivo models, edoxaban is a more effective antithrombotic than fondaparinux. Given orally, the drug rapidly (i.e. in 1–2 hours) reaches its peak plasma concentration and achieves its maximum effect on various antithrombotic biomarkers (e.g. prothrombin time, activated partial thromboplastin time and anti-factor-Xa activity). Edoxaban (15–150 mg once daily) has a linear pharmacokinetic profile. It is readily absorbed when given orally (the bioavailability is 62%), but, unlike other factor-Xa inhibitors, it exhibits only poor binding to plasma proteins and is not biotransformed via CYP3A4. It is eliminated by biliary and renal routes and has a half-life of 10–14 hours, which enables edoxaban to be administered once daily. Exposure to the drug is independent of age, sex and ethnicity, but increases as the patient's weight and renal function decrease.