Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 4 Issue 11

Rivaroxaban and Therapeutic Monitoring Application: Will it be a Significant Tool for Management of COVID-19?

Sara AR1, Eslam MS1, Mohamed Raslan1,2 and Nagwa A Sabri1,2*

1Drug Research Centre, Cairo, Egypt
2Department of Clinical Pharmacy, Faculty of Pharmacy- Ain Shams University, Cairo, Egypt and Principal Investigator of Drug Research Centre, Cairo, Egypt

*Corresponding Author: Nagwa A Sabri, Drug Research Centre and Department of Clinical Pharmacy, Faculty of Pharmacy- Ain Shams University, Cairo, Egypt and Principal Investigator of Drug Research Centre, Cairo, Egypt.

Received: October 03, 2020; Published: October 30, 2020

×

Abstract

Background: SARS-CoV-2 is considered one of the most widely spreaded viral infections globally. Expectation of second wave incidence of Corona virus 2019 is high. Direct inhibitors of factor Xa might be proposed as an adjuvant therapy for coagulation disorders associated with COVID-19.

Aim: Development of a bioanalytical assay for detection of rivaroxaban in human plasma and its pharmacokinetics application including bioavailability studies and monitoring of therapeutic levels to ensure its clinical outcomes as an adjuvant therapy in management of Corona virus 2019 disease.

Method: A protein precipitation technique was used for drug extraction from the plasma by using a mobile phase of 10 mM ammonium acetate pH4.7 and acetonitrile 20:80 V/V at flow rate 0.6 ml/min, ESI positive mode, and m/z 436à144.8, 338à296.2 for rivaroxaban and linezolid (as internal standard)respectively. As a clinical application, a bioequivalence study was conducted in a fully replicated crossover design involving 36 volunteers, where, AUC0-t, AUC0-inf, Cmax, and Tmax were calculated for the assessment of bioequivalence of test and reference products.

Results: The average recovery of Rivaroxaban was 98.675%. The limit of Quantitation was 0.5 ng/ml, and Correlation coefficient (r2) was equal to 0.9999. Statistical analysis of the measured parameters showed that there was no significant difference.

Conclusion: The developed LC/MS/MS bioanalytical method proved to be valid for the determination of rivaroxaban in human plasma and its pharmacokinetics application including comparative bioavailability studies which could be applied for therapeutic levels monitoring of rivaroxaban in management of blood coagulation associated with different diseases including COVID-19.

Keywords: Rivaroxaban; COVID-19; Venous Thromboembolism; LC/MS/MS; Factor Xa; Atrial Fibrillation

×

References

  1. Hu Y., et al. “Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis”. Journal of Clinical Virology 127 (2020): 104371.
  2. Coronavirus disease (COVID-19) Weekly Epidemiological Update. Data as received by WHO from national authorities, as of 10 am CEST 13 September (2020).
  3. Lotfi M., et al. “COVID-19: Transmission, prevention, and potential therapeutic opportunities”. Clinica Chimica Acta 508 (2020): 254-266.
  4. Brayfield A. “Martindale—The Complete Drug Reference”. 38th edn., Pharmaceutical Press, London, UK (2014): 1487.
  5. British National Formulary (BNF) 78. September 2019 – March 2020. Chapter 2 Cardiovascular system, Blood clots, Antithrombotic Drugs (2019): 128.
  6. National Institute for Health and Care Excellence (NICE). Rivaroxaban for preventing atherothrombotic events in people with coronary or peripheral artery disease (TA607) (2019).
  7. Margolis JM., et al. “Shorter Hospital Stays and Lower Costs for Rivaroxaban Compared with Warfarin for Venous Thrombosis Admissions”. Journal of the American Heart Association 10 (2016): e003788.
  8. Bayer HealthCare AG. Clinical Study Synopsis, Rivaroxaban (BAY 59-7939), Study Number: 14588 (2011).
  9. Bayer HealthCare AG. Clinical Study Synopsis, Rivaroxaban (BAY 59-7939), Study Number: 17018 (2015).
  10. Australian Public Assessment Report for prescription medicines (AusPAR). Xarelto Bayer Australia Ltd, PM-2010-03901-3-3 (2012).
  11. Medvedovici A., et al. “Liquid extraction and HPLC-DAD assay of hydrochlorothiazide from plasma for a bioequivalence study at the lowest therapeutic dose”. European Journal of Drug Metabolism and Pharmacokinetics 2 (2000): 91-96.
  12. Dubuc MC., et al. “A Rapid HPLC-DAD Method for Separation and Determination OF Omeprazole Extracted from Human Plasma”. Journal of Liquid Chromatography and Related Technologies8 (2001): 1161-1169.
  13. Zhang YS., et al. “Simultaneous determination and pharmacokinetic studies of dihydromyricetin and myricetin in rat plasma by HPLC-DAD after oral administration of Ampelopsis grossedentata decoction”. Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences1 (2007): 4-9.
  14. Rohde G. “Determination of rivaroxaban-a novel, oral, direct Factor Xa inhibitor-in human plasma by high-performance liquid chromatography-tandem mass spectrometry”. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 872 (2008): 43-50.
  15. Mani H., et al. “Accurate determination of rivaroxaban levels requires different calibrator sets but not addition of antithrombin”. Thrombosis and Haemostasis 108 (2012): 191-198.
  16. Kuhn J., et al. “UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays”. PLOS ONE12 (2015): e0145478.
  17. Korostelev M., et al. “Simultaneous determination of rivaroxaban and dabigatran levels in human plasma by high-performance liquid chromatography-tandem mass spectrometry”. Journal of Pharmaceutical and Biomedical Analysis 100 (2014): 230-235.
  18. Cheng YH., et al. “Rapid determination of rivaroxaban in human urine and serum using colloidal palladium surface-assisted laser desorption/ionization mass spectrometry”. Rapid communications in mass spectrometry: RCM 21 (2015): 1977-1983.
  19. Schellings MW., et al. “Determination of dabigatran and rivaroxaban by ultra-performance liquid chromatography-tandem mass spectrometry and coagulation assays after major orthopaedic surgery”. Thrombosis Research 139 (2016): 128-134.
  20. Reddy GS., et al. “Development and validation of Hplc-Ms/Ms Method for Rivaroxaban quantitation in human plasma using solid phase extraction procedure”. Oriental Journal of Chemistry2 (2016): 1145-1154.
  21. Çelebier M., et al. “Determination of Rivaroxaban in Human Plasma by Solid-Phase Extraction–High Performance Liquid Chromatography”. Journal of Chromatographic Science2 (2015): 216-220.
  22. Varga A., et al. “Rapid liquid chromatography tandem mass spectrometry determination of rivaroxaban levels in human plasma for therapeutic drug monitoring”. Revista Romana de Medicina de Laborator 25 (2017): 145-155.
  23. Zhang WL., et al. “Determination of rivaroxaban, apixaban and edoxaban in rat plasma by UPLC-MS/MS method”. Journal of Thrombosis and Thrombolysis2 (2016): 205-211.
  24. Derogis PBM., et al. “Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS)”. Plos One2 (2017): e0171272.
  25. Draft Guidance on Rivaroxaban (2015).
  26. Guidance for Industry Bioanalytical Method Validation (2018).
  27. Committee for Medicinal Products for Human Use (CHMP). Rivaroxaban film-coated tablets 2.5, 10, 15 and 20mg product-specific bioequivalence guidance, EMA/CHMP/PKWP/151340/2015 (2015).
  28. Kow CS and Hasan SS. “Pharmacologic therapeutic options for thromboprophylaxis in COVID-19”. Journal of Thrombosis and Thrombolysis (2020): 1-2.
  29. Barnett AS., et al. “Net clinical benefit of rivaroxaban compared with warfarin in atrial fibrillation: Results from ROCKET AF”. International Journal of Cardiology 257 (2018): 78-83.
  30. Kow CS., et al. “Management of Outpatient Warfarin Therapy amid COVID-19 Pandemic: A Practical Guide”. American Journal of Cardiovascular Drugs4 (2020): 301-309.
  31. Emert R., et al. “COVID-19 and hypercoagulability in the outpatient setting”. Thrombosis Research 192 (2020): 122-123.
×

Citation

Citation: Nagwa A Sabri., et al. “Rivaroxaban and Therapeutic Monitoring Application: Will it be a Significant Tool for Management of COVID-19?". Acta Scientific Pharmaceutical Sciences 4.11 (2020): 97-105.




Metrics

Acceptance rate32%
Acceptance to publication20-30 days
Impact Factor0.759

Indexed In




News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is July 30, 2021.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US