AIMS: 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. METHODS: We measured the urinary excretion of ATL in 24 patients with both ischaemic heart disease and osteoarthritis, chronically treated withaspirin and co-administered celecoxib 200 mg b.i.d., ibuprofen 600 mg t.i.d., or placebo for 7 days. RESULTS: 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). CONCLUSIONS: 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.
RCT Entities:
AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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