Cyclooxygenase (COX)-2 inhibition has been reported to suppress the biosynthesis of the gastroprotective lipoxygenase metabolite 15(R)-epi-lipoxin A(4), also termed 'aspirin-triggered lipoxin' (ATL). We tested the hypothesis that the co-administration of aspirin with either the selective COX-2 inhibitor celecoxib or the nonselective COX inhibitor ibuprofen reduces ATL biosynthesis.
We measured the urinary excretion of ATL in 24 patients with both ischaemic heart disease and osteoarthritis, chronically treated with aspirin and co-administered celecoxib 200 mg b.i.d., ibuprofen 600 mg t.i.d., or placebo for 7 days.
Baseline ATL was comparable in the three groups. On days 1 and 7, 4 h after co-administration of celecoxib or ibuprofen, ATL levels did not show significant variations (day 1: 0.24 +/- 0.33, 0.26 +/- 0.21 and 0.37 +/- 0.22 ng mg(-1) creatinine, respectively; day 7: 0.21 +/- 0.13, 0.35 +/- 0.15 and 0.23 +/- 0.18 ng mg(-1) creatinine, respectively).
Neither selective nor nonselective COX-2 inhibition appreciably interferes with ATL biosynthesis, suggesting that this mediator is not involved in exacerbating gastrotoxicity by the association of aspirin with COX-2 inhibitors.