ANTIPLATELET EFFECT AND PHARMACOKINETIC COMPARISON OF ORAL VS RECTAL ASPIRIN

据信，血小板聚集部分地负责 心血管疾病的发展，如不稳定型心绞痛， 急性心肌梗塞 阿司匹林减弱血小板聚集， 可能是通过不可逆地抑制环氧化酶， 负责血栓素A（2）的形成，血栓素A（2）是一种有效的刺激剂， 血小板聚集。 阿司匹林已被证明可以显著降低 血管事件的发生率，并广泛建议5月 心血管疾病 许多研究都记录了 速释口服液的药代动力学和抗血小板活性 阿司匹林 然而，目前还没有关于阿司匹林的研究发表。 直肠给药后的药代动力学或药效学 尽管关于直肠给药后水杨酸浓度的信息 行政存在。 这将是一项抗血小板药物的单盲、交叉初步研究。 阿司匹林300 mg单次给药的作用和药代动力学 直肠栓剂和单独的325 mg速释片剂 4个健康的中年人 该项目将实现以下目标： a.比较在一个单一的 阿司匹林口服和直肠给药对离体血小板影响 血栓素B（2）（TXB（2））合成的聚集和抑制 B.比较分布容积，吸收速率常数， 消除速率常数、全身清除率、 可测量的阿司匹林浓度和相对生物利用度 口服和直肠给药的阿司匹林。

It is believed that platelet aggregation is, in part, responsible for the development of cardiovascular diseases such as unstable angina and acute myocardial infarction. Aspirin attenuates platelet aggregation, presumably by irreversibly inhibiting cyclooxygenase, an enzyme responsible for the formation of thromboxane A(2), a potent stimulator of platelet aggregation. Aspirin has been shown to significantly reduce the incidence of vascular events and is widely recommended for may cardiovascular diseases. Numerous studies have documented the pharmacokinetics and antiplatelet activity of immediate-release oral aspirin. However, there have been no published studies of aspirin pharmacokinetics or pharmacodynamics following rectal administration although information on salicylate concentrations following rectal administration does exist. This will be a single-blind, crossover pilot study of the antiplatelet effects and pharmacokinetics of aspirin administered as a single 300 mg rectal suppository and, separately, a 325 mg immediate-release tablet in 4 healthy, middle-aged adults. This project will accomplish the following objectives: a. Compare the onset and magnitude of effects following a single immediate-release oral and rectal dose of aspirin on ex vivo platelet aggregation and suppression of thromboxane B(2) (TXB(2)) synthesis b. Compare the volumes of distribution, absorption rate constants, elimination rate constants, total body clearances, lag times to measurable aspirin concentrations and relative bioavailabilities of orally- and rectally-administered aspirin.