Population pharmacokinetic study and application of ticagrelor and AR-C124910XX after percutaneous coronary intervention in Chinese patients with acute coronary syndrome.

IF 0.9 4区 医学 Q4 PHARMACOLOGY & PHARMACY International journal of clinical pharmacology and therapeutics Pub Date : 2024-09-01 DOI:10.5414/CP204550
Meng Liu, Jun Qin, XiaoQian Chu, NaiDong Chen, Qiong Jie, ShaoJun Zheng
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Abstract

Objectives: This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization.

Materials and methods: Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology.

Results: The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased.

Conclusion: The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.

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中国急性冠脉综合征患者经皮冠状动脉介入治疗后替卡格雷和AR-C124910XX的人群药代动力学研究及应用。
目的:本研究旨在了解中国急性冠脉综合征(ACS)患者服用替卡格雷的药代动力学:本研究旨在了解中国急性冠脉综合征(ACS)患者服用替卡格雷的药代动力学,找出影响因素,为替卡格雷治疗优化提供依据:使用NONMEN分析了195例急性冠脉综合征患者的数据,包括491个血浆替卡格雷浓度时间点和临床信息,并对药代动力学(PK)参数因素进行了分析。结果发现,替卡格雷的PK曲线与其他药物的PK曲线相似:结果:使用一阶吸收速率常数为 0.67/h 的单处置区室模型,ticagrelor 的 PK 曲线得到了很好的描述。当直接胆红素水平和白浆细胞计数升高时,女性患者的肾小球滤过率下降,替卡格雷清除率降低,暴露量增加。当直接胆红素水平升高、体重和血红蛋白降低时,rs6787801为GG的患者与AA和GA相比,替卡格雷代谢物清除率降低,暴露增加:该研究为了解 ACS 患者经皮冠状动脉介入治疗后替卡格雷的剂量-暴露关系提供了重要依据,突出了个性化治疗策略的关键因素。
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来源期刊
CiteScore
1.70
自引率
12.50%
发文量
116
审稿时长
4-8 weeks
期刊介绍: The International Journal of Clinical Pharmacology and Therapeutics appears monthly and publishes manuscripts containing original material with emphasis on the following topics: Clinical trials, Pharmacoepidemiology - Pharmacovigilance, Pharmacodynamics, Drug disposition and Pharmacokinetics, Quality assurance, Pharmacogenetics, Biotechnological drugs such as cytokines and recombinant antibiotics. Case reports on adverse reactions are also of interest.
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