Influence of NSAIDs on Antiplatelet Effects of Aspirin-In vitro Experimental Study Involving NSAID Addition to Human Blood-
Influence of NSAIDs on Antiplatelet Effects of Aspirin-In vitro Experimental Study Involving NSAID Addition to Human Blood-
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NSAIDs 对阿司匹林抗血小板作用的影响-涉及 NSAID 添加到人体血液中的体外实验研究-
DOI：
10.5649/jjphcs.36.382
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
T. Aoyama
中科院分区：
文献类型：
--
作者：
Yuuki Akagi;Kenta Shibata;Yuuta Nio;A. Yanaka;Y. Higami;S. Shimada;T. Aoyama
小剂量阿司匹林通过血小板环氧合酶(COX)-1的不可逆乙酰化作用抑制血小板聚集。非类固醇抗炎药(NSAIDs)具有与阿司匹林相似的作用机制，可能与阿司匹林相互作用。鉴于此，将6种具有不同环氧合酶-1活性的非甾体抗炎药加入到人空白血中，观察其对阿司匹林抗血小板作用的影响。取8名健康志愿者(23.3±3.2岁)，取其富含血小板血浆，分别加入阿司匹林(血浆浓度：16μg/mL)和非甾体抗炎药(临床最大血药浓度)。血小板聚集阈值指数(PATI)作为聚集活性的指标。布洛芬后加阿司匹林组(IBU→Asp)和同时加用阿司匹林组(Asp+IBU)的PATI分别为3.5 4±0.80和3.5 3±1.0 1μg/m L，均低于单用阿司匹林的PATI(5.17±1.18μg/m L)，表明非甾体抗炎药对其抗血小板作用有干扰作用每个非甾体抗炎药(Df)的游离药物浓度(Df)除以血小板COX-1IC50的对数值[log(Df/COX-1IC50)]与其PATI相关(R=0.817，p<；0.001)，提示小剂量阿司匹林与非甾体抗炎药之间的相互作用可能是从临床药物浓度下对血小板COX-1的抑制水平来推断的。
Low dose aspirin acts as an antiplatelet agent through irreversible acetylation of platelet cyclooxygenase (COX)-1,which inhibits platelet aggregation.Nonsteroidal anti-inflammatory drugs (NSAIDs) have a similar mechanism of action to aspirin,and may interact pharmacodynamically with it.In view of this,we performed an in vitro experimental study in which 6 NSAIDs with various COX-1 activities were added to human blank blood to investigate the influence of each one on the antiplatelet action of aspirin.Platelet rich plasma (PRP) was obtained from 8 healthy volunteers (23.3±3.2 years old).After adding aspirin (plasma concn.: 16μg/mL) and NSAIDs (plasma concn.: maximal concentration in clinical use) to the PRP,aggregation was measured using collagen as the stimulus.We used the platelet-aggregation threshold index (PATI) as the index of aggregation activity for this study.The PATI of a group in which aspirin was added after ibuprofen (Ibu→Asp) and that of a group in which both drugs were added at the same time (Asp+Ibu) were 3.54±0.80 and 3.53±1.01μg/mL,respectively.These were lower than the PATI for aspirin alone (5.17±1.18μg/mL),indicating interference with the antiplatelet effect by the NSAID.For the other 5 NSAIDs,the PATI obtained was similar to that for aspirin,regardless of the order of addition.The logarithmic value of the unbound drug concentration of each NSAID (Df) divided by platelet COX-1 IC50[log (Df/COX-1 IC50)]was correlated with its PATI (R=0.817,p<0.001),suggesting that the interaction between low dose aspirin and NSAIDs may be inferred from the level of inhibition of platelet COX-1 at clinical drug concentrations.