替格瑞洛与氯吡格雷在伴有急性冠脉综合征和慢性肾病的患者中的药效学和药代动力学比较。
Pharmacodynamics and pharmacokinetics of ticagrelor vs. clopidogrel in patients with acute coronary syndromes and chronic kidney disease.
机构信息
General Hospital of Shenyang Military Region, Shenyang, China.
出版信息
Br J Clin Pharmacol. 2018 Jan;84(1):88-96. doi: 10.1111/bcp.13436. Epub 2017 Nov 3.
BACKGROUND
Pivotal clinical trials found that ticagrelor reduced ischaemic complications to a greater extent than clopidogrel, and also that the benefit gradually increased with the reduction in creatinine clearance. However, the underlying mechanisms remains poorly explored.
METHODS
This was a single-centre, prospective, randomized clinical trial involving 60 hospitalized Adenosine Diphosphate (ADP) P2Y12 receptor inhibitor-naïve patients with chronic kidney disease (CKD) (estimated glomerular filtration rate <60 ml min 1.73 m ) and non-ST-elevation acute coronary syndromes (NSTE-ACS). Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180 mg loading dose, then followed by 90 mg twice daily) or clopidogrel (600 mg loading dose, then followed by 75 mg once daily). The primary endpoint was the P2Y12 reactive unit (PRU) value assessed by VerifyNow at 30 days. The plasma concentrations of ticagrelor and clopidogrel and their active metabolites were measured in the first 10 patients in each group at baseline, and at 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after the loading dose.
RESULTS
Baseline characteristics were well matched between the two groups. Our results indicated a markedly lower PRU in patients treated with ticagrelor vs. clopidogrel at 30 days (32.6 ± 11.29 vs. 203.7 ± 17.92; P < 0.001) as well as at 2 h, 8 h and 24 h after the loading dose (P < 0.001). Ticagrelor and its active metabolite AR-C124910XX showed a similar time to reach maximum concentration (C ) of 8 h, with the maximum concentration (C ) of 355 (242.50-522.00) ng ml and 63.20 (50.80-85.15) ng ml , respectively. Both clopidogrel and its active metabolite approached the C at 2 h, with a similar C of 8.67 (6.64-27.75) ng ml vs. 8.53 (6.94-15.93) ng ml .
CONCLUSION
Ticagrelor showed much more potent platelet inhibition in comparison with clopidogrel in patients with CKD and NSTE-ACS.
背景
关键性临床试验发现，替格瑞洛降低缺血性并发症的效果优于氯吡格雷，且随着肌酐清除率的降低，其获益逐渐增加。然而，其潜在机制仍未得到充分探索。
方法
这是一项单中心、前瞻性、随机临床试验，纳入了 60 例住院的、对腺苷二磷酸（ADP）P2Y12 受体抑制剂无反应的慢性肾脏病（CKD）（估算肾小球滤过率<60 ml min 1.73 m ）合并非 ST 段抬高型急性冠状动脉综合征（NSTE-ACS）患者。将符合条件的患者以 1:1 的比例随机分为替格瑞洛组（负荷剂量 180 mg，随后每日 90 mg，2 次）或氯吡格雷组（负荷剂量 600 mg，随后每日 75 mg，1 次）。主要终点是 30 天时通过 VerifyNow 评估的 P2Y12 反应单位（PRU）值。在每组的前 10 例患者中，在基线时以及负荷剂量后 1 h、2 h、4 h、8 h、12 h 和 24 h 时，测量替格瑞洛和氯吡格雷及其活性代谢物的血浆浓度。
结果
两组患者的基线特征匹配良好。我们的结果表明，与氯吡格雷相比，替格瑞洛治疗的患者在 30 天时（32.6±11.29 比 203.7±17.92；P<0.001）和负荷剂量后 2 h、8 h 和 24 h 时（P<0.001）的 PRU 明显更低。替格瑞洛及其活性代谢物 AR-C124910XX 达到最大浓度（C ）的时间相似，均为 8 h，最大浓度（C ）分别为 355（242.50-522.00）ng/ml 和 63.20（50.80-85.15）ng/ml。氯吡格雷及其活性代谢物在 2 h 时达到 C ，相似的 C 分别为 8.67（6.64-27.75）ng/ml 比 8.53（6.94-15.93）ng/ml。
结论
与氯吡格雷相比，替格瑞洛在 CKD 和 NSTE-ACS 患者中表现出更强的血小板抑制作用。
Zotero 插件