Herd C M, Rodgers S E, Lloyd J V, Bochner F, Duncan E M, Tunbridge L J
Aust N Z J Med. 1987 Apr;17(2):195-200. doi: 10.1111/j.1445-5994.1987.tb00040.x.
Enteric coated aspirin was given to eight human volunteers in escalating doses (20, 40, 60, 80, 100 mg daily), each dose being given over two weeks. In addition, to measure the maximum effect of aspirin, each volunteer was given two single doses of 600 mg of soluble aspirin. At the end of each dosing interval we measured platelet aggregation and thromboxane formation in response to four aggregating agents and to whole blood coagulation. The doses of aspirin required to inhibit platelet aggregation in response to various stimuli were: for collagen 60-80 mg, for adenosine diphosphate and adrenaline 60 mg, and for arachidonate 40 mg. For maximum inhibition of thromboxane formation the doses were: for collagen greater than 100 mg, for adenosine diphosphate and adrenaline 60 mg, for arachidonate 80 mg, and for whole blood coagulation 100 mg. Different aspirin doses are required to inhibit the responses to different stimuli. Furthermore, for some stimuli, inhibition of thromboxane generation may require more aspirin than is required for inhibition of aggregation. The clinical implications of these findings are uncertain since we do not know which stimuli are important in arterial thrombosis in man.
给八名人类志愿者服用肠溶阿司匹林,剂量逐渐增加(每日20、40、60、80、100毫克),每个剂量服用两周。此外,为了测量阿司匹林的最大效果,给每位志愿者服用两剂600毫克的可溶性阿司匹林。在每个给药间隔结束时,我们测量了血小板聚集和血栓素形成,以应对四种聚集剂和全血凝固。抑制血小板聚集以应对各种刺激所需的阿司匹林剂量为:对胶原蛋白为60 - 80毫克,对二磷酸腺苷和肾上腺素为60毫克,对花生四烯酸为40毫克。为了最大程度抑制血栓素形成,剂量为:对胶原蛋白大于100毫克,对二磷酸腺苷和肾上腺素为60毫克,对花生四烯酸为80毫克,对全血凝固为100毫克。抑制对不同刺激的反应需要不同的阿司匹林剂量。此外,对于某些刺激,抑制血栓素生成可能比抑制聚集需要更多的阿司匹林。由于我们不知道哪些刺激在人类动脉血栓形成中很重要,这些发现的临床意义尚不确定。