替格瑞洛在未使用阿片类药物的 STEMI 和 NSTEMI 中国患者中的药代动力学和药效学。

Ticagrelor Pharmacokinetics and Pharmacodynamics in Chinese Patients with STEMI and NSTEMI Without Opioid Administration.

机构信息

Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Department of Cardiology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, Fujian Province, China.

出版信息

Adv Ther. 2020 Oct;37(10):4220-4232. doi: 10.1007/s12325-020-01423-w. Epub 2020 Aug 8.

DOI:10.1007/s12325-020-01423-w

PMID:32770531

Abstract

INTRODUCTION

The pharmacodynamics (PD) and pharmacokinetics (PK) study of ticagrelor loading dose (LD) in Chinese patients with acute coronary syndrome (ACS) without opioid administration has never been investigated. Therefore, the aim of this study was to evaluate the antiplatelet effects and the PK parameters of ticagrelor in Chinese patients with ACS without opioid administration.

METHODS

A sample size of 30 eligible patients with ACS were enrolled in this study. Blood samples were obtained predose and 1, 2, 4, 8, and 12 h after 180 mg LD of ticagrelor. P2Y reactivity units (PRU) and plasma concentrations of ticagrelor and its two metabolites were measured.

RESULTS

In total, 15 patients were admitted to ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) groups, respectively. For patients with NSTEMI, PRU declined significantly during the first 4 h and maintained a relatively stable antiplatelet effect from 4 to 12 h after LD. A similar trend was found in the STEMI group without significant differences of PRU in each designed time compared with patients with NSTEMI (P > 0.05). T of metabolite AR-C124910XX was 4 h after LD for both groups. There were no significant differences for drug concentration, C, or AUC of ticagrelor and AR-C124910XX between patients with STEMI and NSTEMI (P > 0.05).

CONCLUSIONS

For Chinese patients with ACS, at least 4 h was needed to achieve an adequate antiplatelet effect for ticagrelor LD. There were no differences in PK or PD between Chinese patients with STEMI and NSTEMI.

CLINICAL TRIAL REGISTRATION

ChiCTR1800014764.

摘要

简介

替格瑞洛负荷剂量（LD）在未使用阿片类药物的中国急性冠脉综合征（ACS）患者中的药效学（PD）和药代动力学（PK）研究尚属空白。因此，本研究旨在评估未使用阿片类药物的中国 ACS 患者中替格瑞洛的抗血小板作用和 PK 参数。

方法

本研究纳入了 30 名符合条件的 ACS 患者。在替格瑞洛 180mg LD 给药前和给药后 1、2、4、8 和 12h 采集血样。测量 P2Y 反应单位（PRU）和替格瑞洛及其两种代谢物的血浆浓度。

结果

共有 15 名患者分别入组 ST 段抬高型心肌梗死（STEMI）和非 ST 段抬高型心肌梗死（NSTEMI）组。对于 NSTEMI 患者，PRU 在最初 4h 内显著下降，在 LD 后 4-12h 内保持相对稳定的抗血小板作用。STEMI 组也呈现出类似的趋势，在每个设计时间点的 PRU 与 NSTEMI 患者相比均无显著差异（P＞0.05）。两组的 AR-C124910XX 代谢物 T 为 LD 后 4h。STEMI 和 NSTEMI 患者之间，替格瑞洛和 AR-C124910XX 的药物浓度、C 和 AUC 无显著差异（P＞0.05）。