背景:利伐沙班的几种通用制剂最近上市,可与品牌等同物互换使用。然而,以前没有发表的研究直接比较品牌与品牌的体外抗凝血作用通用利伐沙班。这项体外研究的目的是比较三种原料利伐沙班的效果,从品牌(Xarelto®)和两种通用(Rivarolto®和RivaroxabanSandoz®)利伐沙班制剂在一系列凝血测定中获得。
方法:在正常血浆中掺入几种浓度的三种利伐沙班(范围为50-750ng/ml)。用利伐沙班校准的抗Xa测定法评估浓度,并通过超高效液相色谱-质谱联用串联质谱(UHPLC-MS/MS)确认。进行以下测定:凝血酶原时间(PT),激活部分凝血活酶时间(aPTT),稀释罗素毒蛇毒液测试(dRVVT),凝血酶时间(TT),Clauss纤维蛋白原,因素七,VIII和IX测定,和血栓弹力图.
结果:三种利伐沙班在相似浓度下获得的结果具有可比性。三种利伐沙班浓度的增加与PT呈强正相关,aPTT和dRVVT测定(r>0.95,所有p<0.01),与因子测定呈强负相关(r<-0.95,p<0.01)。TT和Clauss纤维蛋白原不受利伐沙班的影响。在三种利伐沙班获得的平均测定结果中没有发现显着差异。
结论:这项研究表明,品牌利伐沙班和通用利伐沙班在广泛的浓度范围内发挥相同的体外抗凝血作用。
BACKGROUND: Several generic formulations of rivaroxaban were recently marketed to be used interchangeably with their branded equivalent. However, there have been no previously published studies that directly compared the in vitro anticoagulant effect of branded vs. generic rivaroxaban. The aim of this in vitro
study was to compare the effects of three raw rivaroxaban materials, obtained from the branded (Xarelto®) and two generic (Rivarolto® and Rivaroxaban Sandoz®) rivaroxaban formulations on an array of coagulation assays.
METHODS: A pool of normal plasma was spiked with several concentrations of the three rivaroxaban (range 50-750 ng/ml). The concentrations were assessed with a rivaroxaban calibrated anti-Xa assay and confirmed by ultra-high-performance liquid chromatography-mass spectrometry coupled with tandem mass spectrometry (UHPLC-MS/MS). The following assays were performed: Prothrombin time (PT), activated Partial Thromboplastin time (aPTT), Diluted Russell\'s Viper Venom Test (dRVVT), Thrombin time (TT), Clauss Fibrinogen, Factor VII, VIII and IX assays, and thromboelastography.
RESULTS: The results obtained by the three rivaroxaban at similar concentrations were comparable. Increasing concentrations of the three rivaroxaban showed a strong positive correlation with the PT, aPTT and dRVVT assays (r > 0.95, p < 0.01 for all), and a strong negative correlation with the Factors assays (r < -0.95, p < 0.01 for all). TT and Clauss Fibrinogen were not affected by rivaroxaban. No significant difference was identified in the mean assays\' results obtained by the three rivaroxaban.
CONCLUSIONS: This
study showed that the branded and generic rivaroxaban exert an identical in vitro anticoagulant effect across a wide range of concentrations.