Low dose aspirin: selective inhibition of rectal dialysis thromboxane B2 in healthy volunteers

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) B2, prostaglandin (PG) E2 and leukotriene (LT) B2 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 B2, leukotriene B4, prostaglandin E2, and serum thromboxane B2 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 E2 or leukotriene B4, is inhibited by low dose aspirin. We infer that 34% of the rectal thromboxane B2 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.