Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. 
Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran 
is rapid (peak plasma concentrations are reached 4-6 hours following surgery, 
and a further 2 hours later). Its oral bioavailability is low, but shows reduced 
interindividual variability. Dabigatran specifically and reversibly inhibits 
thrombin, the key enzyme in the coagulation cascade. Studies both in healthy 
volunteers and in patients undergoing major orthopaedic surgery show a 
predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant 
effect correlates adequately with the plasma concentrations of the drug, 
demonstrating effective anticoagulation combined with a low risk of bleeding. 
Dabigatran is mainly eliminated by renal excretion (a fact which affects the 
dosage in elderly and in moderate-severe renal failure patients), and no hepatic 
metabolism by cytochrome P450 isoenzymes has been observed, showing a good 
interaction profile. Rivaroxaban will probably be the first available oral 
factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible 
and predictable inhibition of FXa activity with potential to inhibit clot-bound 
FXa. Its pharmacokinetic characteristics include rapid absorption, high oral 
availability, high plasma protein binding and a half-life of aprox. 8 hours. 
Rivaroxaban elimination is mainly renal, but also through faecal matter and by 
hepatic metabolism. Although the drug has demonstrated moderate potential to 
interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major 
CYP450 enzyme.