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Apixaban Metabolism And Pharmacokinetics After Oral Administration To Humans

Nirmala Raghavan, C. Frost, Z. Yu, K. He, H. Zhang, W. Humphreys, D. Pinto, Shiangyuan Chen, S. Bonacorsi, P. Wong, D. Zhang
Published 2009 · Medicine, Chemistry

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The metabolism and disposition of [14C]apixaban, an orally bioavailable, highly selective, and direct acting/reversible factor Xa inhibitor, was investigated in 10 healthy male subjects without (group 1, n = 6) and with bile collection (group 2, n = 4) after a single 20-mg oral dose. Urine, blood, and feces samples were collected from all subjects. Bile samples were also collected for 3 to 8 h after dosing from group 2 subjects. There were no serious adverse events or discontinuations due to adverse effects. In plasma, apixaban was the major circulating component and O-demethyl apixaban sulfate, a stable and water-soluble metabolite, was the significant metabolite. The exposure of apixaban (Cmax and area under the plasma concentration versus time curve) in subjects with bile collection was generally similar to that in subjects without bile collection. The administered dose was recovered in feces (group 1, 56.0%; group 2, 46.7%) and urine (group 1, 24.5%; group 2, 28.8%), with the parent drug representing approximately half of the recovered dose. Biliary excretion represented a minor elimination pathway (2.44% of the administered dose) from group 2 subjects within the limited collection period. Metabolic pathways identified for apixaban included O-demethylation, hydroxylation, and sulfation of hydroxylated O-demethyl apixaban. Thus, apixaban is an orally bioavailable inhibitor of factor Xa with elimination pathways that include metabolism and renal excretion.
This paper references
10.1016/0049-3848(88)90279-4
The inhibition of the generation of thrombin and the antithrombotic effect of a pentasaccharide with sole anti-factor Xa activity.
J. Walenga (1988)
10.1182/BLOOD-2007-03-080838
Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors.
J. Cortes (2007)
10.1001/JAMA.295.13.JOC60038
Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial.
S. Yusuf (2006)
10.1182/BLOOD.V108.11.275.275
Natural course of the subsequent pregnancy after a single loss in women with and without the factor V Leiden or prothrombin 20210A mutations.
M. Coppens (2006)
10.1016/S0049-3848(03)00030-6
Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (fondaparinux).
M. Samama (2003)
Factor Xa inhibitors: today and beyond.
J. Walenga (2003)
10.1007/s00018-002-8415-9
Visions & Reflections Factor Xa - a promising target for drug development
B. Kaiser (2002)
A (2007b) Apixaban, an oral direct, factor Xa inhibitor: single-dose safety, pharmacokinetics and pharmacodynamics in healthy subjects
C Frost (2007)
10.1016/S0049-3848(02)00080-4
Synthetic direct and indirect factor Xa inhibitors.
M. Samama (2002)
10.1111/j.1538-7836.2008.02939.x
Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies
P. Wong (2008)
10.1182/blood.v110.11.4005.4005
The Direct Factor Xa Inhibitor Apixaban Produces Broad Antithrombotic Activity with Limited Effects on Bleeding Time in Rats.
William A. Schumacher (2007)
10.1111/j.1538-7836.2007.02764.x
The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement 1
M. Lassen (2007)
10.2165/00019053-200220090-00004
Direct Medical Cost of Managing Deep Vein Thrombosis According to the Occurrence of Complications
J. O'brien (2012)
Heart disease and stroke statistics-2007 update: a report from the
W Rosamond (2007)
Thromb Haemost 6:1313–1318
J study (2006)
New treatment options for acute coronary syndromes.
C. Campbell (2006)
Bile sampling, processing and analysis in clinical studies.
S. Strasberg (1990)
10.1080/03602530600952172
What is the Objective of the Mass Balance Study? A Retrospective Analysis of Data in Animal and Human Excretion Studies Employing Radiolabeled Drugs
S. Roffey (2007)
Glucuronidation as a major metabolic clearance pathway of [ 14 C ] muraglitazar in humans : different metabolic profiles in subjects with or without bile collection
L Wang (2006)
10.1016/J.JACC.2004.02.051
A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study.
M. Simoons (2004)
10.1182/BLOOD.V108.11.917.917
Effects of the Factor Xa Inhibitor Apixaban on Venous Thrombosis and Hemostasis in Rabbits.
P. Wong (2006)
10.1161/CIRCULATIONAHA.107.187998
Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
W. Rosamond (2007)
10.1002/hep.1840120131
Perinatal hemochromatosis: One disease, several diseases or a spectrum?
J. Collins (1990)
10.1161/CIRCULATIONAHA.106.642074
A Once-Daily, Oral, Direct Factor Xa Inhibitor, Rivaroxaban (BAY 59-7939), for Thromboprophylaxis After Total Hip Replacement
B. Eriksson (2006)
10.1182/BLOOD.V106.11.910.910
Estimated Annual Number of Incident and Recurrent, Non-Fatal and Fatal Venous Thromboembolism (VTE) Events in the US.
J. Heit (2005)
10.1056/NEJMOA055443
Comparison of fondaparinux and enoxaparin in acute coronary syndromes.
S. Yusuf (2006)
10.1517/13543784.15.8.843
Novel factor Xa inhibitors for prevention and treatment of thromboembolic diseases
D. Kubitza (2006)
10.3109/00365529309103136
Is duodenal bile representative of gallbladder bile? A comparative study.
G. Choudhuri (1993)
10.1592/phco.23.6.772.32190
Selective factor Xa inhibition improves efficacy of venous thromboembolism prophylaxis in orthopedic surgery.
Philip C. Comp (2003)
10.1021/JM070245N
Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.
D. Pinto (2007)
Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:e69–e171
W Rosamond (2007)
Efficacy and safety of the oral direct factor
H Büller (2008)
Novel antithrombotic therapies for the prevention of stroke in patients with atrial fibrillation.
M. O'Donnell (2004)
10.1111/j.1538-7836.2008.03054.x
Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose‐ranging study
H. Buller (2008)
10.1002/jps.2600710432
General derivation of the equation for time to reach a certain fraction of steady state.
D. Perrier (1982)
A (2007a) Apixaban, an oral direct, factor Xa inhibitor: multiple ascending-dose safety, pharmacokinetics and pharmacodynamics in healthy subjects
C Frost (2007)
Effective anticoagulation therapy: defining the gap between clinical studies and clinical practice.
A. Wittkowsky (2004)
10.1046/j.1538-7836.2003.00298.x
What is all that thrombin for?
K. Mann (2003)
10.1124/dmd.105.007617
GLUCURONIDATION AS A MAJOR METABOLIC CLEARANCE PATHWAY OF 14C-LABELED MURAGLITAZAR IN HUMANS: METABOLIC PROFILES IN SUBJECTS WITH OR WITHOUT BILE COLLECTION
L. Wang (2006)



This paper is referenced by
10.20452/PAMW.1383
Management of patients who are receiving warfarin or a new oral anticoagulant and require urgent or emergency surgery.
S. Choi (2012)
10.1080/17425255.2019.1604686
Pharmacokinetics and pharmacodynamics of oral anticoagulants used in atrial fibrillation
Ameenathul M. Fawzy (2019)
New Synthetic Antithrombotic for Venous Thromboembolism:, Direct Thrombin Inhibitors, Direct
Xa Inhibitors (2010)
10.1097/WCO.0b013e32834e604a
Stroke prevention in atrial fibrillation: do we still need warfarin?
H C Diener (2012)
10.1016/S0304-5412(12)70485-7
Avances en el tratamiento antitrombótico. Nuevos anticoagulantes orales para reemplazar a acenocumarol (Sintrom
José Antonio Paramo (2012)
10.1517/14656566.2013.774374
Pharmacoeconomic implications of thromboprophylaxis with new oral anticoagulants after total hip or knee replacement in the USA
Edith A Nutescu (2013)
10.4081/ITJM.2013.S8.48
The practical management of bleedings during treatment with direct oral anticoagulants: the emergency reversal therapy
Luca Masotti (2013)
10.1161/STROKEAHA.114.005117
Stroke Prevention in Patients With Atrial Fibrillation and Renal Dysfunction
S. Kaatz (2014)
10.1080/14656566.2016.1232393
Non-vitamin K oral anticoagulants versus vitamin K antagonists in the treatment of venous thromboembolic disease
Christos Voukalis (2016)
10.7150/ijms.34629
Adverse reaction profiles of hemorrhagic adverse reactions caused by direct oral anticoagulants analyzed using the Food and Drug Administration Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database
Kazuyo Shimada (2019)
10.1177/1358863X14534309
The role of novel anticoagulants in the management of venous thromboembolism
Nedaa Skeik (2014)
Efficacia e sicurezza dei nuovi farmaci anticoagulanti orali nella profilassi e nel trattamento del tromboembolismo venoso
L. Masotti (2010)
10.1016/j.clinthera.2015.05.497
Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects.
Y. Song (2015)
10.1136/bcr-2017-221641
Novel oral anticoagulant and kidney injury: apixaban-related acute interstitial nephritis
B. Abdulhadi (2017)
10.1097/FPC.0000000000000294
Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation
S. Ueshima (2017)
10.3949/ccjm.80a.13025
Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban
A. Fawole (2013)
10.1002/psp4.12347
Population Pharmacokinetics of Apixaban in Subjects With Nonvalvular Atrial Fibrillation
B. Cirincione (2018)
10.1345/aph.1Q119
The Role of Apixaban for Venous and Arterial Thromboembolic Disease
Rathasen Prom (2011)
10.1007/978-1-4471-4336-9_6
New Drugs for Thromboprophylaxis: Apixaban, Dabigatran, Rivaroxaban
Raquel Ferrandis (2013)
10.1080/14740338.2019.1676723
A drug safety evaluation of apixaban for the treatment of atrial fibrillation, acute coronary syndrome, and percutaneous coronary intervention
Jakub Gumprecht (2019)
10.1016/j.suc.2018.05.005
Rapid Reversal of Novel Anticoagulant and Antiplatelet Medications in General Surgery Emergencies.
Lisa L. Schlitzkus (2018)
10.1007/s40265-016-0644-6
Apixaban: A Review in Venous Thromboembolism
Sarah L Greig (2016)
10.1586/ehm.10.5
Novel oral anticoagulants for prophylaxis and treatment of venous thromboembolism: part I (Factor Xa inhibitors)
Rohtesh S Mehta (2010)
10.1007/s40262-012-0030-9
New Oral Anticoagulants: Comparative Pharmacology with Vitamin K Antagonists
F. Scaglione (2013)
10.3346/jkms.2019.34.e160
Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer
Jang Ho Lee (2019)
10.4155/bio.14.66
LC-MS/MS determination of apixaban (BMS-562247) and its major metabolite in human plasma: an application of polarity switching and monolithic HPLC column.
J. Pursley (2014)
10.2147/CPAA.S51981
Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
Yi-min Cui (2013)
10.2147/DDDT.S6074
New anticoagulants for the prevention of venous thromboembolism
C. Becattini (2010)
10.1093/eurheartj/ehy136
The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
J. Steffel (2018)
10.2147/TCRM.S24238
Efficacy and safety of venous thromboembolism prophylaxis with apixaban in major orthopedic surgery
S. Werth (2012)
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
J. Eikelboom (2014)
10.1161/ATVBAHA.114.303400
Clinical Experience With Novel Oral Anticoagulants for Thromboprophylaxis After Elective Hip and Knee Arthroplasty
C. Messerschmidt (2015)
See more
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