The influence of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban-an oral, direct factor xa inhibitor

Journal of Clinical Pharmacology

Volumn 53, Issue 3, 2013, Pages 249-255

  Kubitza, Dagmar ^a   Becka, Michael ^a   Roth, Angelika ^a   Mueck, Wolfgang ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

Age; Gender; Pharmacodynamics; Pharmacokinetics; Rivaroxaban

Indexed keywords

PLACEBO; RIVAROXABAN;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; FEMALE; HUMAN; HUMAN EXPERIMENT; KIDNEY FUNCTION; MALE; NORMAL HUMAN; PROTHROMBIN TIME; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE;

ADULT; AGE FACTORS; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; FACTOR XA; FEMALE; HUMANS; MALE; MORPHOLINES; SEX FACTORS; THIOPHENES; YOUNG ADULT;

EID: 84877846026     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.5     Document Type: Article

References (34)

1. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:630S-669S.
2. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133: 381S-453S.
3. Harrington RA, Becker RC, Cannon CP, et al. Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:670S-707S.
4. Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:454S-545S.
5. Heeringa J, van der Kuip DAM, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27:949-953.
6. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370-2375.
7. Anderson FA, Jr., Wheeler HB, Goldberg RJ, et al. A populationbased perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med. 1991;151:933-938.
8. Spencer FA, Gore JM, Lessard D, et al. Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost. 2008;100:780-788.
9. Engbers MJ, van Hylckama Vlieg A, Rosendaal FR. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost. 2010;8:2105-2112.
10. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007; 5:692-699.
11. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29:2276-2315.
12. Schulman S. Current strategies in prophylaxis and treatment of venous thromboembolism. Ann Med. 2008;40:352-359.
13. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:160S-198S.
14. Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141:745-752.
15. Garcia D, Regan S, Crowther M, Hughes RA, Hylek EM. Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. Chest. 2005;127: 2049-2056.
16. Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther. 2005;78:412-421.
17. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939-an oral, direct Factor Xa inhibitor-after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873-880.
18. Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin. 2008;24:2757-2765.
19. Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans. Drug Metab Dispos. 2009;37:1056-1064.
20. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765-2775.
21. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a doubleblind, randomised controlled trial. Lancet. 2008;372:31-39.
22. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776-2786.
23. Turpie AGG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673-1680.
24. Rohde G. Determination of rivaroxaban-A novel, oral, direct Factor Xa inhibitor-in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;872:43-50.
25. Bayer Pharma AG. Xarelto (rivaroxaban) Summary of Product Characteristics. 2012. Available at: http://www.xarelto. com/html/downloads/ Xarelto-Prescribing-Information-Nov-2012. pdf. Accessed January 9, 2013.
26. Glassock RJ, Winearls C. Ageing and the glomerular filtration rate: truths and consequences. Trans Am Clin Climatol Assoc. 2009;120: 419-428.
27. Mueck W, Borris LC, Dahl OE, et al. Population pharmacokinetics and pharmacodynamics of once-and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost. 2008;100:453-461.
28. Mueck W, Lensing AW, Agnelli G, Decousus H, Prandoni P, Misselwitz F. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet. 2011;50:675-686.
29. Kubitza D, Becka M, Mueck W, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban-an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2010;70:703-712.
30. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365:883-891.
31. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-2510.
32. Turpie AGG, Lassen MR, Eriksson BI, et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost. 2011;105:444-453.
33. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19.
34. Fox KAA, Piccini JP, Wojdyla D, et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J. 2011;32:2387-2394.