Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban – an oral, direct Factor Xa inhibitor – in healthy subjects

Rapid liquid chromatography tandem mass spectrometry determination of rivaroxaban levels in human plasma for therapeutic drug monitoring

“…Isolated use of p-glycoprotein inhibitors/ inducers, however, does not seem to significantly affect rivaroxaban pharmacokinetics [19]. Although rivaroxaban appears to have low variability, pharmacokinetic studies reported high interindividual variations in drug plasma levels, even among apparently healthy individuals [20]. In patients with venous thromboembolism, both peak (22 μg/L to 535 μg/L) and trough (6 μg/L to 239 μg/L) rivaroxaban levels varied widely, although the clinical impact of these variations has not been reported yet [21].…”

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

“…Factor Xa activities do not completely return to baseline at 24 h for doses above 5 mg (Kubitza et al, 2005). Inhibition of Factor Xa activity and prolongation of the prothrombin time correlate with rivaroxaban plasma concentrations (Mueck et al, 2007). Rivaroxaban has a dual mode of elimination, with approximately two-thirds undergoing metabolic degradation in the liver, of which half is excreted via the kidneys and the other half via the hepatobiliary route.…”

New Antithrombotic Drugs

“…118 Rivaroxaban: A direct factor Xa inhibitor, rivaroxaban is an active compound with about 80% oral bioavailability. Plasma levels of rivaroxaban peak 2 to 3 h after administration, and the terminal halflife is 7 to 11 h. 119,120 Rivaroxaban is eliminated by the kidneys and in the feces. One-third of the administered drug is cleared as unchanged active drug by the kidneys, one-third is metabolized by the liver via CYP3A4-dependent and CYP3A4-independent pathways and then excreted in feces, and one-third is metabolized to inactive metabolites, which are then excreted by the kidneys.…”