Department of Pharmacy, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore, 768828, Singapore.
Consultant Cardiologist, Sarawak Heart Centre, Kuching - Samarahan Expressway, 94300, Kota Samarahan, Sarawak, Malaysia.
J Thromb Thrombolysis. 2018 Nov;46(4):541-548. doi: 10.1007/s11239-018-1726-y.
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 PT and PT are moderately correlated with Cmin,ss (r = 0.43) and Cmax,ss (r = 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.
本研究的目的是比较亚洲人和白种人利伐沙班的稳态谷浓度(Cmin,ss)和峰浓度(Cmax,ss),并评估利伐沙班浓度与凝血酶原时间/国际标准化比值(PT/INR)之间的关系。入组患者被建议服用利伐沙班的时间。当患者到达时,采集 Cmin,ss 和 PT/INR。患者在用餐时服用利伐沙班后 2 至 4 小时抽取 Cmax,ss 和 PT/INR。分析纳入 30 例患者:男性占 57%(n=17),女性占 43%(n=13),20mg 组占 77%(n=23),15mg 组占 23%(n=7)。中位 PT 和 INR 与 Cmin,ss(r=0.43)和 Cmax,ss(r=0.49)中度相关。服用 15mg 的患者的 Cmin,ss 和 Cmax,ss 低于白种人[12ng/ml 比 57ng/ml(Cmin,ss);87ng/ml 比 229ng/ml(Cmax,ss),均 p<0.01]。服用 20mg 的患者的 Cmin,ss 和 Cmax,ss 也低于白种人[14ng/ml 比 44ng/ml(Cmin,ss);101ng/ml 比 249ng/ml(Cmax,ss),均 p<0.01]。亚组分析显示 BMI≥30 的患者的 Cmax,ss 低于 BMI<30 的患者[80.47ng/ml 比 124ng/ml(p=0.014)]。新加坡患者的 Cmin,ss 和 Cmax,ss 低于白种人。这可能会影响利伐沙班在新加坡患者中的有效性。BMI 较高的患者可能不会像 BMI 较低的患者那样受益。最后,Dade Innovin 试剂测定的 INR 对利伐沙班浓度的变化不敏感。