Introduction: Factor Xa
metabolites in faeces.18
of apixaban accounts for approximately 27% of total clearance. Additional biliary and intestinal excretion has also been described.
Edoxaban is another highly specific, direct oral inhibitor of Factor Xa, with an approximate 10,000-fold selectivity for Factor Xa over thrombin.19
In a single-
dose study in healthy subjects, the maximum plasma concentration of 60mg edoxaban was observed at 1.5 hours after administration, corresponding to the maximum inhibition of Factor Xa activity, which returned to baseline levels by 12 hours. The half-life is 10–14 hours; plasma protein binding is 40–60%.20
Rivaroxaban reversibly binds to the catalytic pocket of Factor Xa, thereby inhibiting its coagulant activity.13,14
competitively inhibits Factor Xa and is 10,000-fold more selective for Factor Xa than other related serine proteases. Unlike indirect Factor Xa inhibitors, rivaroxaban inhibits both free- and clot-bound Factor Xa. The bioavailability of rivaroxaban is high (>80%) and the maximum concentration is observed two to four hours after oral intake.13
extensively (>90%) bound to plasma proteins, and its maximum plasma concentration is dose dependent. The half-life ranges from five to nine hours and the kidneys excrete 66% of the orally ingested drug.15
Other modes of
excretion involve faecal elimination and hepatic metabolism.
Factor Xa is a crucial element of the coagulation cascade. With its unique position in the coagulation pathway and its critical role in the initiation of thrombin generation, Factor Xa has emerged as an attractive target for anticoagulation. The availability of the new generation of specific
anticoagulants, including the oral direct Factor Xa inhibitors, has resulted in a paradigm shift in anticoagulation, both for stroke prevention in atrial fibrillation as well as the treatment and long-term prevention of venous thromboembolism. l
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12. Bauer KA. Fondaparinux: a new synthetic and selective inhibitor of Factor Xa. Best Pract Res Clin Haematol 2004;17:89–104.
13. Perzborn E et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939 – an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005;3: 514–21.
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15. Kubitza D et al. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005;78:412–21.
16. He K et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor. Eur J Drug Metab Pharmacokinet 2011;36:129–39. 17. Pinto DJP et al. Discovery of
1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin- 1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c] pyridine-3-carboxamide (apixaban, BMS- 562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J Med Chem 2007;50:5339–56.
18. Raghavan N et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009;37:74–81.
19. Furugohri T et al. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. Thromb Haemost 2008;6:1542–9.
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