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Effects of the Oral, Direct Factor Xa Inhibitor Rivaroxaban on Platelet‐Induced Thrombin Generation and Prothrombinase Activity 1
Author(s) -
Graff Jochen,
Hentig Nils,
Misselwitz Frank,
Kubitza Dagmar,
Becka Michael,
Breddin HansKlaus,
Harder Sebastian
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007302952
Subject(s) - rivaroxaban , prothrombinase , thrombin , pharmacology , coagulation , chemistry , clotting time , tissue factor , platelet , medicine , atrial fibrillation , warfarin
Rivaroxaban (BAY 59‐7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo‐controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5‐ or 30‐mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase‐induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase‐induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen‐induced endogenous thrombin potential was reduced by ∼80% and ∼90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor‐induced endogenous thrombin potential was reduced by ∼40% (5 mg) and ∼65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase‐induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet‐induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma.