The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factorXa inhibitor, in healthy subjects
Open accessAbstract
AIM: Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. METHOD: This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels - apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily- with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). RESULTS: Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ~3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3-1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration-time profile. CONCLUSION: Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Hence, the more favorable bleeding profile is proposed to be a result of the decreased peak-to-trough ratios afforded by twice-daily DOAC dosing. 19”
From Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world (2019) · cites this paper as [19]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
American Psychiatric Association (2000) · doi:10.1176/appi.books.9780890423349 · Cited by 11,069
Apixaban versus warfarin in patients with atrial fibrillation
Granger, C. B., Alexander, J. H., McMurray, J. J. V., Lopes, R. D., Hylek, E. M., Hanna, M., Al-Khalidi, H. R., Ansell, J., Atar, D., Avezum, A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107039 · Cited by 8,943
Kearon (2012) · doi:10.1378/chest.11-2301 · Cited by 6,119
Apixaban in patients with atrial fibrillation
Connolly, S. J., Eikelboom, J., Joyner, C., Diener, H.-C., Hart, R., Golitsyn, S., Flaker, G., Avezum, A., Hohnloser, S. H., Diaz, R., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1007432 · Cited by 2,483
Lassen, M. R., Raskob, G. E., Gallus, A., Pineo, G., Chen, D., & Hornick, P. (2010) · The Lancet · doi:10.1016/s0140-6736(09)62125-5 · Cited by 777
Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement
Lassen, M. R., Gallus, A., Raskob, G. E., Pineo, G., Chen, D., & Ramirez, L. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006885 · Cited by 775
Apixaban or Enoxaparin for Thromboprophylaxis after Knee Replacement
Lassen, M. R., Raskob, G. E., Gallus, A. S., Pineo, G. F., Chen, D., & Portman, R. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810773 · Cited by 694
Stangier, J. (2008) · Clinical Pharmacokinetics · doi:10.2165/00003088-200847050-00001 · Cited by 659
Structure-Based Design of Novel Potent Nonpeptide Thrombin Inhibitors
Hauel, N. H., Nar, H., Priepke, H. W. M., Ries, U. J., Stassen, J., & Wienen, W. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0109513 · Cited by 457
Roehrig, S., Straub, A., Pohlmann, J., Lampe, T. F. J., Pernerstorfer, J., Schlemmer, K., Reinemer, P., & Perzborn, E. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050101d · Cited by 440
Cited by
Sorted by citations
Steffel, J., Collins, R., Antz, M., Cornu, P., Desteghe, L., Haeusler, K. G., Oldgren, J., Reinecke, H., Roldan-Schilling, V., Rowell, N., et al. (2021) · EP Europace · doi:10.1093/europace/euab065 · Cited by 1,132
Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants
Cuker, A. C., Siegal, D. M., Crowther, M. A., & Garcia, D. A. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.05.065 · Cited by 455
Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH
Martin, K. A., Beyer‐Westendorf, J., Davidson, B. L., Huisman, M. V., Sandset, P. M., & Moll, S. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13323 · Cited by 450
Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications
Narouze, S., Benzon, H. T., Provenzano, D. A., Buvanendran, A., Andrés, J. A. D., Deer, T. R., Rauck, R. L., & Huntoon, M. A. (2015) · Regional Anesthesia & Pain Medicine · doi:10.1097/aap.0000000000000223 · Cited by 366
Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review
Byon, W., Merali, S. J., Boyd, R. A., & Frost, C. E. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00775-z · Cited by 373
Self-citation
Metadata
- Authors
- Frost, C., Nepal, S., Wang, J., Schuster, A., Byon, W., Boyd, R. A., Yu, Z., Shenker, A., Barrett, Y. C., Mosqueda‐Garcia, R., & LaCreta, F.
- Affiliations
- Princeton University (US)
- Pfizer (United States) (US)
- Corresponding author
- Frost, Charles
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2013-10-21
- Volume
- 76
- Issue
- 5
- Pages
- 776-786
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC3853536
- OpenAlex
- W1568662837
- Cited by
- 286
- References
- 35
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 14 · 2023: 23 · 2022: 15 · 2021: 30 · 2020: 22 · 2019: 23 · 2018: 20 · 2017: 24 · 2016: 34 · 2015: 30 · 2014: 19 · 2013: 11
- FWCI
- 21.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer Inc
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- apixaban, factor Xa inhibitors, pharmacokinetics, pharmacodynamics, multiple oral doses, dose escalation, safety and tolerability, anticoagulation, international normalized ratio, activated partial thromboplastin time, prothrombin time, steady-state concentration, peak-to-valley ratio, dosing regimen
- MeSH terms
- Administration, Oral, Adult, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Fibrinolytic Agents, Humans, Male, Partial Thromboplastin Time, Prothrombin Time, Pyrazoles, Pyridones, International Normalized Ratio, Young Adult, Factor Xa Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
