Pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor.
Anticoagulants have a key role in the management of venous and arterial thromboembolic disorders. Traditional anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are effective but have limitations that make the management of thromboembolic disorders difficult. There is a clear need for new anticoagulants that are at least as effective as traditional agents but without their drawbacks. This review discusses the mechanism of action, pharmacokinetics, and pharmacodynamics of one of these newer agents - the direct Factor Xa inhibitor rivaroxaban - and provides an overview of the results of phase III clinical studies. Based on these results, rivaroxaban has gained approval for the prevention and treatment of several thromboembolic disorders in adult patients. Rivaroxaban, which has a rapid onset of action, targets free and clot-bound Factor Xa and Factor Xa in the prothrombinase complex. It reaches maximal plasma concentration 2-4 hours after administration and has a high bioavailability (80-100%). Rivaroxaban has several advantages over traditional anticoagulants. It does not require dose adjustment for age, sex, body weight, or ethnicity, and there is no requirement for routine coagulation monitoring because it has been shown to have predictable pharmacokinetics and pharmacodynamics. Furthermore, rivaroxaban has minimal food and drug interactions. The introduction of newer oral anticoagulants, such as rivaroxaban, that are convenient to administer and have predictable pharmacokinetic and pharmacodynamic profiles, could ultimately simplify patient management in clinical practice and may improve clinical outcomes across a broad range of thromboembolic disorders.
Department of Clinical Pharmacology and Toxicology, Charité, Universitätsmedizin - Berlin, Charitéplatz 1, 10117 Berlin, Germany. reinhold.kreutz@charite.de.
Reinhold
R
Kreutz
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017326:Clinical Trials, Phase III as Topic; D004347:Drug Interactions; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D013923:Thromboembolism / Q000517:prevention & control
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban