首页> 外文期刊>Journal of thrombosis and thrombolysis >Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients
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Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients

机译:与低体重患者相比,接受氯吡格雷维持治疗的体重较高的患者活动代谢产物浓度较低,血小板抑制水平较低,且对不良反应的发生率较高

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Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, 60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow? P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p 0.001), and VASP-PRI (56 ± 18 vs. 39 ± 17, p 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9 %) and VASP-PRI (65 vs. 27 %). Body weight correlated with PRU and VASP-PRI (both p 0.001), and inversely with log transformed AUC(0-tlast) (p 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel.
机译:体重是氯吡格雷反应的预测指标。但是,尚无前瞻性研究根据体重比较药效学(PD)和药代动力学(PK)数据。我们比较了75 mg氯吡格雷对稳定冠心病低体重(LBW,<60 kg)和较高体重(HBW,≥60kg)患者的PD和PK效果。 LBW(n = 34,56.4±3.7 kg)和HBW(n = 38,84.7±14.9 kg)阿司匹林治疗的患者接受75 mg氯吡格雷治疗10-14天。通过非隔室方法计算通过直至服药后4 h的最后可量化浓度AUC(0-tlast)计算的活性代谢物(Clop-AM)浓度-时间曲线下的面积。透光聚集法(LTA)(最大血小板聚集和抑制血小板聚集至20μM二磷酸腺苷(ADP),残留血小板聚集至5μMADP),VerifyNow?进行P2Y12反应单位(PRU)和血管扩张剂相关的刺激的磷蛋白磷酸化血小板反应性指数(VASP-PRI)。 HBW患者的平均AUC(0-tlast)低于LBW患者:12.8对17.9 ng h / mL。通过LTA(所有p≤0.01),PRU(207±68 vs. 152±57,p <0.001)和VASP-PRI(56±18 vs. 39±17,p <0.001)测量,HBW患者的血小板反应性更高)。使用PRU(35 vs. 9%)和VASP-PRI(65 vs. 27%),更多的HBW患者表现出较高的治疗中血小板反应性(HPR)。体重与PRU和VASP-PRI相关(均p <0.001),与对数转换的AUC(0-tlast)成反比(p <0.001)。总之,与LBW患者相比,HBW患者的Clop-AM水平较低,血小板反应性和HPR率较高,这导致他们对氯吡格雷的反应欠佳。

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