Arthritis Center Twente, University Twente and Medisch Spectrum Twente, 7500KA Enschede, Netherlands.
Eur J Clin Pharmacol. 2013 Mar;69(3):365-71. doi: 10.1007/s00228-012-1370-y. Epub 2012 Aug 14.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function.
Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation.
Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold.
COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect.
在患有伤害感受性疼痛和心血管合并症的患者中，经常同时开具非甾体抗炎药（NSAIDs）和乙酰水杨酸（ASA）。 NSAIDs 和 ASA 抑制相同的 COX 酶，因此可能会相互作用。 ASA 的抗血小板作用完全依赖 COX-1。 NSAIDs 可以是非 COX-1 和 COX-2 选择性的，也可以是 COX-2 选择性的。本研究的目的是研究 ASA 与不同选择性和非选择性 NSAIDs 对血小板功能的相互作用。
在 30 名健康志愿者中进行了为期 3 天的周期、双盲、前瞻性、安慰剂对照、体外、序贯交叉试验，每个周期之间有至少 12 天的洗脱期，评估在 ASA 前 2 小时服用萘普生、布洛芬、美洛昔康或依托考昔对 ASA 抗血小板作用的相互作用。使用血小板功能分析仪 100（PFA-100）测量体外血小板功能、以秒为单位的闭合时间（CT）。周期中 CT 的延长反映了血小板抑制作用。ASA 无反应定义为安慰剂周期中 CT 延长<40%。排除 ASA 无反应者。使用 Wilcoxon 符号秩检验评估 NSAID 对 ASA 诱导的 CT 延长的影响。
布洛芬和萘普生抑制 ASA 抗血小板作用低于无反应阈值。依托考昔和美洛昔康不会导致 ASA 血小板抑制作用的相关变化。萘普生在 ASA 反应阈值以下具有固有的弱血小板抑制作用。
COX-1 亲和力决定了 NSAIDs 和 ASA 对血小板黏附和聚集的相互作用。在 ASA 前 2 小时服用布洛芬和萘普生会显著抑制 ASA 的抗血小板作用，但依托考昔和美洛昔康不会。
