Rosenkranz B, Frölich J C
Prostaglandins Leukot Med. 1985 Sep;19(3):289-300. doi: 10.1016/0262-1746(85)90142-8.
The present study has investigated whether low-dose acetylsalicylic acid (ASA) can inhibit platelet aggregation locally at its site of gastrointestinal absorption without concentrations in the systemic circulation high enough for inhibition of cyclooxygenase. For this purpose platelet aggregation, thromboxane formation as well as ASA plasma concentrations were measured in 8 volunteers before oral intake of 100 mg ASA as well as 20 to 300 minutes thereafter. At each time 5 ml of blood were mixed with 5 ml of blood obtained from a second, untreated volunteer. Aggregation and thromboxane formation were also determined in these mixed blood samples. The same protocol was performed with 4 volunteers after administration of 1500 mg ASA as well as after no drug intake. In a separate experiment the concentration-effect-relationship of ASA was assessed in vitro. One hundred and forty minutes after administration of 100 mg ASA aggregation and thromboxane formation were significantly decreased to 49.4 and 4.5% of the initial values, respectively, whereas in the mixed blood sample aggregation was not impaired. Inhibition of thromboxane formation was constantly 73% of the inhibition observed in the unmixed sample throughout the study period and thus most probably was caused by dilution of the platelets of the untreated volunteer by the inactivated platelets of the ASA-treated volunteer. These data suggest the absence of pharmacologically active drug concentrations in the peripheral blood. ASA plasma concentration was highest after 40 minutes (2.2 +/- 1.6 microgram/ml; n = 5). After the 1500 mg ASA dose platelet function and thromboxane formation decreased to 29.8 and 2.0% of the initial values, respectively. Furthermore, aggregation and thromboxane formation in the mixed blood sample were markedly reduced. Thus, after the high dose of ASA effective plasma concentrations were present in the peripheral circulation. Highest ASA plasma concentrations were 21.1 +/- 8.9 micrograms/ml. IC50 values were 1.00 +/- 0.36 and 0.30 +/- 0.05 microgram/ml for aggregation and thromboxane formation in vitro, respectively. It is concluded that low dose ASA can effectively inhibit platelet function without producing pharmacologically active concentrations in the peripheral circulation.
本研究调查了低剂量乙酰水杨酸（ASA）是否能在胃肠道吸收部位局部抑制血小板聚集，而不会在体循环中产生足以抑制环氧化酶的浓度。为此，在8名志愿者口服100mg ASA之前以及之后20至300分钟测量血小板聚集、血栓素形成以及ASA血浆浓度。每次取5ml血液与从另一名未治疗的志愿者获取的5ml血液混合。这些混合血液样本中也测定了聚集和血栓素形成。4名志愿者在服用1500mg ASA后以及未服用药物后按照相同方案进行操作。在一项单独实验中，体外评估了ASA的浓度-效应关系。服用100mg ASA后140分钟，聚集和血栓素形成分别显著降低至初始值的49.4%和4.5%，而在混合血液样本中聚集未受损害。在整个研究期间，血栓素形成的抑制作用始终为未混合样本中观察到的抑制作用的73%，因此很可能是由于服用ASA的志愿者的失活血小板稀释了未治疗志愿者的血小板所致。这些数据表明外周血中不存在具有药理活性的药物浓度。ASA血浆浓度在40分钟后最高（2.2±1.6微克/毫升；n = 5）。服用1500mg ASA剂量后，血小板功能和血栓素形成分别降至初始值的29.8%和2.0%。此外，混合血液样本中的聚集和血栓素形成明显降低。因此，高剂量ASA后外周循环中存在有效的血浆浓度。最高ASA血浆浓度为21.1±8.9微克/毫升。体外聚集和血栓素形成的IC50值分别为1.00±0.36和0.30±0.05微克/毫升。结论是低剂量ASA可有效抑制血小板功能，而不会在外周循环中产生具有药理活性的浓度。
