Brandon R A, Emmett J A, Eadie M J, Curran A C, Bunce I H
Thromb Haemost. 1986 Apr 30;55(2):222-7.
In a random cross-over design, six healthy consenting adult volunteers were given on separate occasions single doses of 300-650 mg of 3 different formulations of enteric-coated aspirin. Over various intervals for 48-54 h following dosage, plasma aspirin and salicylate concentrations were measured together with percentage inhibition of platelet aggregation activated by threshold concentrations of sodium arachidonate alone and combined with ADP and collagen. In all subjects each formulation delivered measurable quantities of aspirin to the peripheral circulation, the unchanged drug being detected at various times up to and including 28 h after dosage. Moreover, low aspirin concentrations were found to co-exist with unimpaired platelet aggregation. All 3 formulations yielded statistically significant (P less than 0.01) inhibition of platelet aggregation activated both by arachidonate and by the combination of aggregants when tested 24-29 and 48-54 h after dosage; there were no significant differences (P greater than 0.05) between the 3 formulations in this regard. Two different patterns of delivery of unchanged aspirin to the systemic circulation from these enteric-coated formulations were apparent. These patterns may be important when considering which aspirin formulation might be most appropriate in chronic use for an antiplatelet effect. None of the enteric-coated formulations used in this study may be optimal in this regard.
在一项随机交叉设计中,六名健康且同意参与的成年志愿者在不同时间分别单次服用300 - 650毫克三种不同剂型的肠溶阿司匹林。在给药后的48 - 54小时内的不同时间段,测量血浆中阿司匹林和水杨酸酯的浓度,以及单独使用花生四烯酸钠阈值浓度激活的血小板聚集抑制百分比,还有联合使用ADP和胶原激活的血小板聚集抑制百分比。在所有受试者中,每种剂型都能将可测量量的阿司匹林输送到外周循环,在给药后长达28小时(包括28小时)的不同时间都能检测到未代谢的药物。此外,发现低浓度的阿司匹林与未受影响的血小板聚集同时存在。在给药后24 - 29小时和48 - 54小时进行测试时,所有三种剂型对花生四烯酸钠和联合聚集剂激活的血小板聚集均产生了具有统计学意义(P小于0.01)的抑制作用;在这方面,三种剂型之间没有显著差异(P大于0.05)。从这些肠溶制剂向体循环输送未代谢阿司匹林有两种不同模式。在考虑哪种阿司匹林剂型最适合长期用于抗血小板作用时,这些模式可能很重要。在这方面,本研究中使用的任何一种肠溶制剂可能都不是最佳的。