Ortega-Paz Luis, Franchi Francesco, Rollini Fabiana, Galli Mattia, Been Latonya, Ghanem Ghussan, Shalhoub Awss, Ossi Tiffany, Rivas Andrea, Zhou Xuan, Pineda Andres M, Suryadevara Siva, Soffer Daniel, Zenni Martin M, Mahowald Madeline K, Langaee Taimour, Jakubowski Joseph A, Cavallari Larisa H, Angiolillo Dominick J
Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.
Maria Cecilia Hospital, GVM Care and Research, Cotignola, Italy.
JACC Basic Transl Sci. 2024 Mar 25;9(7):865-876. doi: 10.1016/j.jacbts.2024.03.003. eCollection 2024 Jul.
This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite. In vitro PD assessments were conducted on baseline samples incubated with escalating concentrations of clopidogrel and its active metabolite. Among patients with diabetes mellitus treated with clopidogrel, impaired renal function was associated with increased maximum platelet aggregation. This finding could be attributed partially to upregulation of the P2Y activity without differences in drug absorption or metabolism. (Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus; NCT03774394).
这项前瞻性体外和体内药效学（PD）/药代动力学研究在患有（n = 31）和未患有慢性肾病（n = 30）的糖尿病患者中进行。PD评估包括血小板反应指数、最大血小板聚集率和P2Y反应单位。体外药代动力学评估包括氯吡格雷及其活性代谢物的血浆水平。体外PD评估是在与递增浓度的氯吡格雷及其活性代谢物孵育的基线样本上进行的。在接受氯吡格雷治疗的糖尿病患者中，肾功能受损与最大血小板聚集率增加有关。这一发现可能部分归因于P2Y活性上调，而药物吸收或代谢无差异。（慢性肾病对糖尿病患者氯吡格雷疗效的影响；NCT03774394）
