摘要
目的观察人类重组促红细胞生成素(促红素,抗贫血药)对阿司匹林和氯吡格雷抗血小板作用的影响。方法采取随机、双盲、安慰剂对照的研究方法,将96例健康志愿者随机分成4组(每组24例),分别静脉注射促红素100、200、400 u·kg^(-1)以及安慰剂,每日1次共3天;在第3天最后1次促红素静脉注射后即刻,所有志愿者随机(1:1)口服单剂量的阿司匹林325 mg或氯吡格雷300 mg;在促红素首次剂量前、口服阿司匹林或氯吡格雷后5 h及1、5、7天后,检测出血时间、血小板功能以及血清促红素水平、凝血指标和血小板激活的细胞因子等。结果与安慰剂组相比,在各检测时间点,100、200 u·kg^(-1)促红素均未影响阿司匹林和氯吡格雷延长出血时间和对血小板功能的作用;400 u·kg^(-1)促红素在志愿者口服阿司匹林后5 h和1天,显著阻滞了阿司匹林延长出血时间的作用(P=0.03),在给药5天后显著增加了血小板的数量(P=0.014);但并未影响其对血小板功能(PFA)封闭时间的作用;对氯吡格雷的作用也无影响。结论短时间静脉应用400 u·kg^(-1)促红素可减弱阿司匹林和氯吡格雷的抗血小板作用。
Objective To evaluate whether or not the recombinant human erythropoietin （rHuEpo） would mitigate the anti -platelet effects of aspirin and clopidogrel. Methods rHuEpo 100,200,400 u · kg^-1, or placebo was given intravenously once daily to 96 healthy subjects for 3 consecutive days in a double - blind, placebo - controlled, randomized trial （n = 24 per group）. A single oral dose of aspirin 325 mg or clopidogrel 300 mg was given immediately after the last dose of rHuEpo administration. In vivo （ bleeding time） and in vitro platelet functions （ PFA -100 closure time） were determined before 5 h and 1, 5,7 days after aspirin or clopidogrel. Results rHuEpo at doses of 100 and 200 u · kg^-1 did not alter bleeding time or PFA -100 closure times at any time point when compared with placebo, rHuEpo at a dose of 400 u · kg^-1 significantly blunted the post -aspirin increase in bleeding time when compared with placebo （P = 0.03 ）, but did not alter post - clopidogrel bleeding times, nor PFA closure times. The 400 u · kg^-1 dose did not change hematocrit, but did significantly increase the platelet count at 5 days after study drug administration when compared with placebo （P = 0. 014）. Conclusion Short -term rHuEpo at dose of 400 u · kg^-1 mitigated the anti - platelet effects of aspirin or clopidogrel in healthy subjects.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2008年第6期483-489,共7页
The Chinese Journal of Clinical Pharmacology
