Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers
Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers
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DOI：
10.2147/cpaa.s47895
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发表时间：
2014-01-01
影响因子：
2
通讯作者：
Hohlfeld, T.
中科院分区：
文献类型：
--
作者：
Nagelschmitz, J.;Blunck, M.;Hohlfeld, T.
工作背景：在一项随机、安慰剂对照、交叉研究中评估了静脉注射（250或500 mg）或口服（100、300或500 mg）单剂量乙酰水杨酸（阿萨）的药理学。方法：在22名健康志愿者服用阿萨之前和之后24小时内采集血液和尿液样本。使用经验证的技术确定药代动力学参数和血小板聚集的测量值。给药途径之间的比较显示，几何平均剂量校正峰浓度（C-max/D）和几何平均剂量校正曲线下面积与口服给药相比，阿萨500 mg静脉给药后的AUC（0-无穷大）/D更高（估计比率分别为11.23和2.03）。两种阿萨静脉给药均在5分钟内实现血小板聚集的完全抑制，反映了口服给药未观察到的快速抑制作用。在给药后5分钟，静脉注射阿萨250 mg和阿萨500 mg时，花生四烯酸诱导的血栓烷B-2合成的离体平均减少率分别为99.3%和99.7%。在探索性分析中，静脉注射ASA 500 mg与口服阿萨500 mg相比，血栓烷B2合成显著降低（P
Background: The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study.Methods: Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques.Results: A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (C-max/D) and the geometric mean dose-corrected area under the curve (AUC(0-infinity)/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B-2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P