Aspirin-triggered lipoxin in patients treated with aspirin and selective vs. nonselective COX-2 inhibitors.
OBJECTIVE
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.
'G. d'Annunzio' University, Chieti, Italy.
Giulia
G
Renda
Maria
M
Zurro
Mario
M
Romano
Raffaele
R
De Caterina
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D044045:Lipoxins / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010003:Osteoarthritis / Q000188:drug therapy*; D015990:Placebo Effect; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage
D052246:Cyclooxygenase 2 Inhibitors; D044045:Lipoxins; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D001241:Aspirin; D007052:Ibuprofen