Presystemic Acetylation of Platelets by Aspirin: Reduction in Rate of Drug Delivery to Improve Biochemical Selectivity for

The utility of aspirin in the treatment of vascular occlusive disease has been ascribed to its blockade of platelet thromboxane A2 (TXA2), a potent inhibitor of vascular smooth muscle contraction and platelet aggregation. Coincident with the inhibition of TxA2 by aspirin at currently used dose regimens is a decrease in formation of prostacyclin (PGI2), an eicosanoid with opposing effects to TxA2 in vWo. The coincident inhibition of PGI2 could potentially limit the therapeutic efficacy of aspirin. This study addressed the issue as to whether a reduction in the rate of drug delivery could enhance the biochemical selectivity of aspirin toward inhibition of TxA2. lntubation studies were performed in parallel groups of healthy volunteers in which a 50-mg aspirin dose was administered as either a bolus or a 5 or 10 mg/hr infusion via a nasogastnc tube. A control group received buffe