Bucchi F, Bodzenta A, de Gaetano G, Cerletti C
Prostaglandins. 1986 Nov;32(5):691-701. doi: 10.1016/0090-6980(86)90191-7.
Aspirin inhibits cyclo-oxygenase, thus preventing prostanoids formation. After oral administration aspirin is hydrolysed to inactive salicylate partly within the gastrointestinal tract, partly during first pass in the liver, partly in the circulation by plasma esterases. Intravenous aspirin, in contrast, mainly undergoes plasma esterase-catalysed deacetylation. Six healthy male subjects were given 1 g aspirin orally and intravenously two weeks apart according to a cross-over randomized design. Whereas serum TxB2 generation reflecting platelet cyclo-oxygenase activity was suppressed by aspirin by both routes, urinary excretion of TxB2 and 6-keto-PGF1 alpha was not affected by oral aspirin, but was partially though significantly reduced by the i.v. drug. Drug disposition seems therefore to be essential in determining the "biochemical selectivity" of aspirin as related to platelet and renal prostanoids generation.
阿司匹林抑制环氧化酶，从而阻止前列腺素的形成。口服后，阿司匹林部分在胃肠道内、部分在肝脏首过过程中、部分在循环中经血浆酯酶水解为无活性的水杨酸盐。相比之下，静脉注射的阿司匹林主要经血浆酯酶催化进行脱乙酰化。按照交叉随机设计，6名健康男性受试者每隔两周分别口服和静脉注射1g阿司匹林。虽然通过两种途径给予的阿司匹林均抑制了反映血小板环氧化酶活性的血清TXB2生成，但口服阿司匹林不影响TXB2和6-酮-PGF1α的尿排泄，而静脉注射该药则使其部分但显著减少。因此，药物处置似乎对于确定阿司匹林与血小板和肾脏前列腺素生成相关的“生化选择性”至关重要。
