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Prostaglandins (PG) are synthesized by two isoforms of the enzyme PG G/H synthase [cyclooxygenase (COX)]. To examine selectivity of tolerated doses of an inhibitor of the inducible COX-2 in humans, we examined the effects of celecoxib on indices of COX-1-dependent platelet thromboxane (Tx) A₂ and on systemic biosynthesis of prostacyclin in vivo. Volunteers received doses of 100, 400, or 800 mg of celecoxib or 800 mg of a nonselective inhibitor, ibuprofen. Ibuprofen, but not celecoxib, significantly inhibited TxA₂-dependent aggregation, induced ex vivo by arachidonic acid (83 ± 11% vs. 11.9 ± 2.2%; P < 0.005) and by collagen. Neither agent altered aggregation induced by thromboxane mimetic, U46619. Ibuprofen reduced serum TxB₂ (−95 ± 2% vs. −6.9 ± 4.2%; P < 0.001) and urinary excretion of the major Tx metabolite, 11-dehydro TxB₂ (−70 ± 9.9% vs. −20.3 ± 5.3%; P < 0.05) when compared with …