Journal of Thrombosis and Thrombolysis

, Volume 46, Issue 4, pp 541–548 | Cite as

Comparison of rivaroxaban concentrations between Asians and Caucasians and their correlation with PT/INR

  • Hobart Owen Ng TsaiEmail author
  • Janice Jia Ni Goh
  • Jernice Wan Xin Aw
  • Yingying Lin
  • Alan Yean Yip Fong
  • Lee Len Tiong
  • Doreen Su-Yin Tan


The objectives of this study are to compare steady-state trough (Cmin,ss) and peak (Cmax,ss) concentrations of rivaroxaban between Asians and Caucasians and to evaluate the relationship between rivaroxaban concentrations and prothrombin time/international normalized ratio (PT/INR). Recruited patients were advised on the time to take rivaroxaban. Cmin,ss and PT/INR were taken when patients arrived. Cmax,ss and PT/INR were drawn between 2 and 4 h later after the patient took rivaroxaban with food. Thirty patients were included in the analyses: 57% (n = 17) males and 43% (n = 13) females, 77% (n = 23) on 20 mg and 23% (n = 7) on 15 mg. Median PTtrough and PTpeak are moderately correlated with Cmin,ss (r2 = 0.43) and Cmax,ss (r2 = 0.49), respectively. Patients on 15 mg have lower Cmin,ss and Cmax,ss versus Caucasians [12 ng/ml vs. 57 ng/ml (Cmin,ss); 87 ng/ml vs. 229 ng/ml (Cmax,ss), p < 0.01 for both]. Patients on 20 mg also have lower Cmin,ss and Cmax,ss versus Caucasians [14 ng/ml vs. 44 ng/ml (Cmin,ss); 101 ng/ml vs. 249 ng/ml (Cmax,ss), p < 0.01 for both]. Subgroup analysis shows patients with BMI ≥ 30 have lower Cmax,ss than patients with BMI < 30 [80.47 ng/ml vs. 124 (p = 0.014)]. Cmin,ss and Cmax,ss were lower in Singaporeans than Caucasians. This may have an impact on the effectiveness of rivaroxaban in Singaporeans. Patients with higher BMI may not benefit similarly as patients with lower BMI. Lastly, the Dade Innovin reagent’s measure of PT/INR is not sensitive towards changes in rivaroxaban concentrations.


Rivaroxaban Plasma concentration PT INR Asian 



Dr. Wang Jiexun for her help with the statistics. Dr. Ong Hean Yee, Dr. Lee Chee Wan, Dr. Ling Lee Fong, Dr. Leow Khang Leng, Dr. Dinna Soon Kar Nee, Dr. Michael Liang Mao Chen, Dr. Syed Saqib Imran, Dr. Justin Tang I-Shing, Dr. Cliff Wong Chun Pong, Dr. Ramkumar Sekar for letting us recruit your patients. Ms. Soh Lay See for extending a hand to help us with the logistics of the study.


This study was funded by National Medical Research Council (NRMC) Centre Grant Pitch-For-Fund. Award No: PFF15001.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

This study was approved by the Domain Specific Review Board (DSRB) prior to the commencement of the study (DSRB approval reference number: 2016/00195).

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Tanigawa T, Kaneko M, Hashizume K et al (2013) Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation. Drug Metab Pharmacokinet 28(1):59–70CrossRefPubMedGoogle Scholar
  2. 2.
    Hori M, Matsumoto M, Tanahashi N et al (2012) Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation—the J-ROCKET AF study. Circ J 76(9):2104–2111CrossRefPubMedGoogle Scholar
  3. 3.
    Kreutz R (2014) Pharmacokinetics and pharmacodynamics of rivaroxaban–an oral, direct factor Xa inhibitor. Curr Clin Pharmacol 9(1):75–83CrossRefPubMedGoogle Scholar
  4. 4.
    Samama MM, Contant G, Spiro TE et al (2013) Laboratory assessment of rivaroxaban: a review. Thromb J 11(1):11CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891CrossRefPubMedGoogle Scholar
  6. 6.
    Reilly PA, Lehr T, Haertter S et al (2014) The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (randomized evaluation of long-term anticoagulation therapy). J Am Coll Cardiol 63(4):321–328CrossRefPubMedGoogle Scholar
  7. 7.
    Eikelboom JW, Connolly SJ, Brueckmann M et al (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369(13):1206–1214CrossRefPubMedGoogle Scholar
  8. 8.
    Camm AJ, Amarenco P, Haas S et al (2016) XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 37(14):1145–1153CrossRefPubMedGoogle Scholar
  9. 9.
    First Pan-Asian Real-World Study on the use of once daily direct factor Xa inhibitor for stroke prevention in patients with atrial fibrillation In: Bayer: science for a better life global news. Accessed 17 Jan 2018
  10. 10.
    Streiff MB, Agnelli G, Connors JM et al (2016) Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis 41(1):32–67CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mueck W, Stampfuss J, Kubitza D, Becka M (2014) Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet 53(1):1–16CrossRefPubMedGoogle Scholar
  12. 12.
    Ahmed S, Zhou Z, Zhou J, Chen SQ (2016) Pharmacogenomics of drug metabolizing enzymes and transporters: relevance to precision medicine. Genom Proteom Bioinform 14(5):298–313CrossRefGoogle Scholar
  13. 13.
    Ozen F, Silan C, Uludag A et al (2011) Association between ABCB1 (MDR1) gene 3435 C> T polymorphism and colchicine unresponsiveness of FMF patients. Ren Fail 33(9):899–903CrossRefPubMedGoogle Scholar
  14. 14.
    Zhao X, Sun P, Zhou Y et al (2009) Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects. Br J Clin Pharmacol 68(1):77–88CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Van dyk M, Marshall JC, Sorich MJ, Wood LS, Rowland A (2018) Assessment of inter-racial variability in CYP3A4 activity and inducibility among healthy adult males of Caucasian and South Asian ancestries. Eur J Clin Pharmacol 74(7):913–920CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyKhoo Teck Puat HospitalSingaporeSingapore
  2. 2.Consultant CardiologistSarawak Heart CentreKota SamarahanMalaysia
  3. 3.Clinical Research Centre, Sarawak General HospitalJalan HospitalKuchingMalaysia

Personalised recommendations