Aspirin-triggered lipoxin in patients treated with aspirin and selective vs. nonselective COX-2 inhibitors

Br J Clin Pharmacol. 2010 Mar;69(3):303-6. doi: 10.1111/j.1365-2125.2009.03579.x.

Abstract

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.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Aspirin / pharmacology*
  • Celecoxib
  • Cyclooxygenase 2 Inhibitors / administration & dosage*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Ibuprofen / administration & dosage
  • Lipoxins / biosynthesis*
  • Lipoxins / metabolism
  • Lipoxins / pharmacology
  • Middle Aged
  • Myocardial Ischemia / drug therapy*
  • Osteoarthritis / drug therapy*
  • Placebo Effect
  • Pyrazoles / administration & dosage
  • Sulfonamides / administration & dosage

Substances

  • Cyclooxygenase 2 Inhibitors
  • Lipoxins
  • Pyrazoles
  • Sulfonamides
  • Celecoxib
  • Aspirin
  • Ibuprofen