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Low dose aspirin: selective inhibition of rectal dialysis thromboxane B 2 in healthy volunteers
Author(s) -
COLE A. T.,
FILIPOWICZ B.,
HYMANTAYLOR P.,
HAWKEY C. J.
Publication year - 1994
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1994.tb00325.x
Subject(s) - medicine , aspirin , dialysis , thromboxane , pharmacology , thromboxane a2 , platelet
SUMMARY Aim: To investigate the degree and selectivity of rectal thromboxane inhibition by low dose aspirin and there by investigate the contribution of platelet thromboxane to rectal thromboxane. Methods: The study was a randomized double‐blind placebo controlled crossover study. Twelve healthy volunteers were studied, each over four separate study periods with two weeks wash‐out between each period. Changes in levels of thromboxane (TX) B 2 , prostaglandin (PG) E 2 and leukotriene (LT) B 2 in rectal dialysates were measured in response to 5 days oral low dose aspirin therapy in one of three once‐daily formulations (plain 75 mg, plain 300 mg or enteric coated 300 mg), and compared to placebo. For each study period, rectal dialysates (4 h duration) were obtained at baseline and twice more after 5 days of aspirin or placebo therapy. Dialysate levels of thromboxane B 2 , leukotriene B 4 , prostaglandin E 2 , and serum thromboxane B 2 were measured by radioimmunoassay. Results: Dialysate thromboxane B, levels were consistently inhibited by low dose aspirin (overall results of all formulations, 75 to 300 mg daily) from 1.06 ng/ml (geometric mean, 95 % CI:0.79–1.43 ng/ml) on placebo, by 29% (95% CI: 11–40%) to 0.75 ng/ml(0.56–1.01 ng/ml) ( P = 0.046) on aspirin. In the absence of aspirin the level of prostaglandin E, was 1.47 ng/ml (0.97–2.23 ng/ml) and in the presence of aspirin was not significantly changed. The dialysate level of leultotriene B, was 0.45 ng/ml(0.34–0.61 ng/ml) in the absence of aspirin and there was no significant change on low dose aspirin. Serum thromboxane was inhibited by 80% to 20% of placebo values by plain aspirin 75 mg, by 95 % by plain aspirin 300 mg, and by 82 % by enteric coated aspirin 300 mg, respectively ( P < 0.01). These results show that 29 % of the rectal thromboxane, but none of the rectal prostaglandin E 2 or leukotriene B 4 , is inhibited by low dose aspirin. We infer that 34% of the rectal thromboxane B 2 is platelet‐derived in our volunteers. Conclusion: Low dose aspirin will selectively inhibit a proportion of rectal thromboxane and may have prophylactic therapeutic potential in inflammatory bowel disease.