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.
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