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Erschienen in: Journal of Thrombosis and Thrombolysis 4/2018

28.08.2018

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

verfasst von: Hobart Owen Ng Tsai, Janice Jia Ni Goh, Jernice Wan Xin Aw, Yingying Lin, Alan Yean Yip Fong, Lee Len Tiong, Doreen Su-Yin Tan

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 4/2018

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Abstract

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.
Literatur
1.
Zurück zum Zitat 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):59–70CrossRefPubMed 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):59–70CrossRefPubMed
2.
Zurück zum Zitat 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):2104–2111CrossRefPubMed 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):2104–2111CrossRefPubMed
3.
Zurück zum Zitat Kreutz R (2014) Pharmacokinetics and pharmacodynamics of rivaroxaban–an oral, direct factor Xa inhibitor. Curr Clin Pharmacol 9(1):75–83CrossRefPubMed Kreutz R (2014) Pharmacokinetics and pharmacodynamics of rivaroxaban–an oral, direct factor Xa inhibitor. Curr Clin Pharmacol 9(1):75–83CrossRefPubMed
5.
Zurück zum Zitat Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891CrossRefPubMed Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891CrossRefPubMed
6.
Zurück zum Zitat 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):321–328CrossRefPubMed 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):321–328CrossRefPubMed
7.
Zurück zum Zitat Eikelboom JW, Connolly SJ, Brueckmann M et al (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369(13):1206–1214CrossRefPubMed Eikelboom JW, Connolly SJ, Brueckmann M et al (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369(13):1206–1214CrossRefPubMed
8.
Zurück zum Zitat 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):1145–1153CrossRefPubMed 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):1145–1153CrossRefPubMed
10.
Zurück zum Zitat 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):32–67CrossRefPubMedPubMedCentral 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):32–67CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Mueck W, Stampfuss J, Kubitza D, Becka M (2014) Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet 53(1):1–16CrossRefPubMed Mueck W, Stampfuss J, Kubitza D, Becka M (2014) Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet 53(1):1–16CrossRefPubMed
12.
Zurück zum Zitat 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):298–313CrossRef 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):298–313CrossRef
13.
Zurück zum Zitat 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):899–903CrossRefPubMed 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):899–903CrossRefPubMed
14.
Zurück zum Zitat 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):77–88CrossRefPubMedPubMedCentral 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):77–88CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat 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):913–920CrossRefPubMed 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):913–920CrossRefPubMed
Metadaten
Titel
Comparison of rivaroxaban concentrations between Asians and Caucasians and their correlation with PT/INR
verfasst von
Hobart Owen Ng Tsai
Janice Jia Ni Goh
Jernice Wan Xin Aw
Yingying Lin
Alan Yean Yip Fong
Lee Len Tiong
Doreen Su-Yin Tan
Publikationsdatum
28.08.2018
Verlag
Springer US
Erschienen in
Journal of Thrombosis and Thrombolysis / Ausgabe 4/2018
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-018-1726-y

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