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在急性心肌梗死二级预防的AMIS、PARIS和德奥试验中使用的原始乙酰水杨酸制剂的血浆药物和抗血小板谱。

Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS, PARIS and German-Austrian trials for secondary prevention of myocardial infarction.

作者信息

Simrock R, Rehders K, Spahn H, Mutschler E, Breddin H K

机构信息

Department of Internal Medicine, Faculty of Pharmacy and Biochemistry, J. W. Goethe University, Frankfurt, Main, Federal Republic of Germany.

出版信息

Eur J Clin Pharmacol. 1988;33(6):541-7. doi: 10.1007/BF00542484.

Abstract

In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.

摘要

在一项交叉研究中,6名健康男性受试者按照阿司匹林心肌梗死研究(AMIS)、潘生丁 - 阿司匹林再梗死研究(PARIS)以及德奥二级心脏病发作预防试验中使用的乙酰水杨酸(ASA)制剂的原始研究方案,服用这些制剂9天。在每个用药期的第一天重复研究ASA及其主要代谢产物水杨酸(SA)和水杨尿酸(SUA)的血浆浓度,以及血小板功能(胶原诱导的血小板聚集;组织提取物诱导的血小板形状变化),并在第六天和第九天再次进行检查。仅在第一天发现了ASA及其代谢产物血浆浓度的差异,这可能是由于吸收速率不同所致。制剂吸收越快,胶原诱导的血小板聚集受到的抑制就越迅速。每种ASA制剂从第一剂起就抑制了组织提取物诱导的血小板形状变化,尽管仅在AMIS制剂中观察到具有统计学意义的抑制作用。得出的结论是,所测试的各种ASA制剂的抗血栓形成效率差异不能通过其药代动力学和抗血小板特性的差异来解释。

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