[Pharmacokinetics and pharmacodynamics of the new oral anticoagulants @entity3926 and XXXX ].

@entity1 @entity8 @entity556 @entity548 @entity3926 @entity177 @entity14534 @entity3925 @entity6236
@entity3926 is the first available oral direct @entity556 inhibitor anticoagulant. Absorption of the prodrug, @entity14534 and its conversion to @entity3926 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. @entity3926 specifically and reversibly inhibits @entity556 , the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in @entity1 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 @entity548 . @entity3926 is mainly eliminated by @entity8 (a fact which affects the dosage in elderly and in moderate-severe @entity177 @entity1 ), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. @entity3925 will probably be the first available oral @entity6236 ( @entity6236 ) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of @entity6236 activity with potential to inhibit clot-bound @entity6236 . 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.
