Mohri H, Ohkubo T
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Ann Pharmacother. 1993 Apr;27(4):405-10. doi: 10.1177/106002809302700401.
To evaluate the effect of a single dose of enteric-coated aspirin (ECA) in three different dosages on platelet function and thromboxane generation in middle-aged men.
In a nonblind, nonplacebo-controlled, crossover study, a single dose of ECA (50, 250, or 1000 mg) was given in a tablet form to a group of healthy, middle-aged men. Ten subjects, aged 50-67 years, volunteered to participate in this study. Platelet functions including bleeding time, platelet aggregation, adenine nucleotides, beta-thromboglobulin, platelet factor 4, thromboxane generation, and aspirin measurement were determined.
Before ECA ingestion, the intracellular adenine nucleotides (adenosine triphosphate, adenosine diphosphate) were decreased, and both beta-thromboglobulin and platelet factor 4 were increased. These observations suggested that platelets were activated in vivo in middle-aged men. These findings returned to normal within 8 hours after the ingestion of ECA, and maintained normal for at least two days. Bleeding time was significantly prolonged at 8 and 24 hours compared with that before ingestion of ECA 1000 mg (p < 0.05). The generation of platelet thromboxane was maximally inhibited by approximately 40 percent in the samples 8 hours after ECA ingestion. Abnormal values of adenine nucleotides, beta-thromboglobulin, and platelet factor 4 returned to normal within 8 hours. Arachidonic acid-induced platelet aggregation was inhibited compared with that before treatment (p < 0.01) and the inhibitory effect was maintained for at least three days. Adenosine diphosphate- and epinephrine-induced aggregations were less inhibited than those induced by arachidonic acid. Inhibitory effects of ECA on platelet aggregation were dose dependent.
Our study indicates that platelets are activated in middle-aged men and that a single dose of ECA 50 mg is safe and can inhibit thromboxane synthesis and platelet aggregation. These results suggest that a daily dose of ECA 50 mg may be useful for blocking platelet activation and preventing thrombosis.
评估三种不同剂量的单剂量肠溶阿司匹林（ECA）对中年男性血小板功能和血栓素生成的影响。
在一项非盲、非安慰剂对照的交叉研究中，以片剂形式给一组健康中年男性服用单剂量的ECA（50、250或1000毫克）。10名年龄在50 - 67岁的受试者自愿参与本研究。测定了包括出血时间、血小板聚集、腺嘌呤核苷酸、β - 血小板球蛋白、血小板因子4、血栓素生成和阿司匹林测量在内的血小板功能。
在摄入ECA之前，细胞内腺嘌呤核苷酸（三磷酸腺苷、二磷酸腺苷）减少，β - 血小板球蛋白和血小板因子4均增加。这些观察结果表明中年男性体内血小板被激活。这些发现摄入ECA后8小时内恢复正常，并至少维持两天正常。与摄入1000毫克ECA前相比，8小时和24小时时出血时间显著延长（p < 0.05）。ECA摄入后8小时的样本中，血小板血栓素的生成最大程度被抑制约40%。腺嘌呤核苷酸、β - 血小板球蛋白和血小板因子4的异常值在8小时内恢复正常。与治疗前相比，花生四烯酸诱导的血小板聚集受到抑制（p < 0.01）且抑制作用至少维持三天。二磷酸腺苷和肾上腺素诱导的聚集比花生四烯酸诱导的聚集受抑制程度小。ECA对血小板聚集的抑制作用呈剂量依赖性。
我们的研究表明中年男性体内血小板被激活，且单剂量50毫克的ECA是安全的，可抑制血栓素合成和血小板聚集。这些结果表明每日剂量50毫克的ECA可能有助于阻止血小板激活和预防血栓形成。
