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  • Title: Low-dose enteric-coated aspirin: a practical approach to continuous-release low-dose aspirin and presystemic acetylation of human platelet cyclooxygenase.
    Author: Jakubowski JA, Stampfer MJ, Vaillancourt R, Faigel D, Deykin D.
    Journal: J Lab Clin Med; 1986 Dec; 108(6):616-21. PubMed ID: 3097223.
    Abstract:
    Using a granular enteric-coated aspirin (ECA) preparation, we achieved continuous release of low-dose aspirin and associated inhibition of platelet reactivity. The lowest once-daily dose that produced greater than 90% inhibition of serum thromboxane (TX) A2 after 7 days was 80 mg. The time course of inhibition after the first dose indicated a gradual release of aspirin over a period of 8 hours. We subsequently fractionated this 80 mg dose into three times daily doses of 27 mg that were administered to nine healthy men for 7 days. This regimen resulted in 96% inhibition of serum TXA2 generation (P less than 0.001), inhibition of in vitro platelet aggregation (P less than 0.05), prolongation of the bleeding time by 75% (P less than 0.01), and a threefold increase in inhibition of platelet aggregation by prostacyclin (P less than 0.01) compared with pre-ECA values. In contrast to our previous study using daily 80 mg doses of ECA, after the 27 mg three times daily regimen we found a significant increase in circulating platelet cyclooxygenase activity 24 hours after the final dose (P less than 0.05). This immediate recovery indicates active megakaryocyte cyclooxygenase and suggests that acetylation of platelet cyclooxygenase was restricted to the presystemic circulation. We conclude that long-term dosing with 27 mg ECA three times daily results in profound inhibition of platelet TXA2 production, and diminished in vitro and in vivo platelet reactivity. This regimen provides a practical approach to achieving continuous release of low-dose aspirin and possible presystemic acetylation of platelet cyclooxygenase.
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