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Ticagrelor pharmacokinetics and pharmacodynamics in patients with NSTEMI after a 180-mg loading dose

机译：180mg加载剂量后Nstemi患者的TicagreloR药代动力学和药效学

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The pharmacokinetics after a 180-mg loading dose (LD) of ticagrelor has not been thoroughly investigated in NSTEMI patients. We aimed to compare the ticagrelor uptake and on-treatment platelet reactivity between non-ST-segment elevation myocardial infarction (NSTEMI) patients and a control group of patients with stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention. We performed an observational, prospective, single-center study including 40 NSTEMI patients and 20 SCAD controls. Key exclusion criteria included ongoing opioid treatment. Both groups received a 180-mg ticagrelor LD, and blood samples were taken pre-dose and 1, 2, 3, 4, 5, and 6 hours post-LD. Plasma concentrations of ticagrelor and its active metabolite AR-C124910XX were determined by validated methods. Platelet aggregation was tested using ADP-induced multiple electrode aggregometry. The primary endpoint was the time to maximal ticagrelor concentration (T-max). Clinical trial registration identifier number: NCT02292277. None of the pharmacokinetic variables differed significantly between the groups, including the T-max of ticagrelor (2.0h [1.0-3.0] versus 2.0h [2.0-3.0], p = 0.393) and the active metabolite AR-C124910XX (3.0 [2.0-4.0] versus 3.0 [2.5-4.0], p = 0.289). High on-treatment platelet reactivity (HPR) was defined as > 46 aggregation units and was at one hour seen in 15% of the NSTEMI patients versus 10% of the controls (p = 1.0). At two hours post the 180-mg ticagrelor LD, 3% of the NSTEMI patients had HPR compared with none of the controls (p = 1.0). In conclusion, the uptake of ticagrelor was not significantly slower in NSTEMI patients not receiving opioids compared with the SCAD controls, leading to adequate onset of platelet inhibition in both groups.
机译：在Nstemi患者中尚未彻底研究180mg加载剂量（LD）后的药代动力学。我们旨在比较非ST段抬高心肌梗死（NSTemi）患者（Nstemi）患者（Nstemi）患者与稳定冠状动脉疾病患者对照组的治疗血小板反应性，接受精神经经皮冠状动脉介入的稳定冠状动脉疾病患者。我们进行了一个观察性，前瞻性单中心的研究，包括40名NSTemi患者和20名SCAD对照。关键排除标准包括正在进行的阿片类药物治疗。两组接受了180mg TiCagreloR LD，血液样品均为后剂量和1,2,3,4,5和6小时。通过验证方法测定TicagreloLoR的血浆浓度及其活性代谢物Ar-C124910xx。使用ADP诱导的多电极聚集体测试血小板聚集。主要终点是最大TiCagreler浓度（T-MAX）的时间。临床试验登记标识符号：NCT02292277。这些药代动力学变量没有显着不同，包括TiCagreloLoR的T-Max（2.0H [1.0-3.0]，p = 0.393）和活性代谢物AR-C124910xx（3.0 [2.0] -4.0]对3.0 [2.5-4.0]，p = 0.289）。高治疗血小板反应性（HPR）定义为> 46聚集单元，并在15％的NSTemi患者中看到的1小时，而不是10％的对照（P = 1.0）。在两小时后，180毫克Ticagrelel LD，3％的NSTemi患者与任何对照相比有HPR（P = 1.0）。总之，与苏尔邦尔对照相比，NSTemi患者的TicagreloR的摄取并没有显着较慢，导致两组血小板抑制的充分发作。

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