Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease.
Clin Pharmacol Ther
; 80(3): 264-74, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16952493
ABSTRACT
BACKGROUND AND OBJECTIVE:
We performed a placebo-controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)-1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease.METHODS:
Twenty-four patients who were undergoing long-term treatment with aspirin (100 mg daily) for cardioprotection were coadministered celecoxib, 200 mg twice daily, ibuprofen, 600 mg 3 times daily, or placebo for 7 days.RESULTS:
The coadministration of placebo or celecoxib did not undermine the aspirin-related inhibition of platelet COX-1 activity, as assessed by measurements of serum thromboxane B(2) (TXB(2)) levels, as well as platelet function. In contrast, a significant (P < .001) increase in serum TXB(2) level was detected on day 7 before drug administration (median, 19.13 ng/mL [range, 1-47.5 ng/mL]) and at 24 hours after the coadministration of aspirin and ibuprofen (median, 22.28 ng/mL [range, 4.9-44.4 ng/mL]) versus baseline (median, 1.65 ng/mL [range, 0.55-79.8 ng/mL]); this was associated with a significant increase in arachidonic acid-induced platelet aggregation (P < .01) and adenosine diphosphate-induced platelet aggregation (P < .05) and a decrease in the time to form an occlusive thrombus in the platelet function analyzer (P < .01). The urinary excretion of 11-dehydro-TXB(2), an index of systemic thromboxane biosynthesis, was not significantly affected by the coadministration of treatment drugs. At steady state, a comparable and persistent inhibition of lipopolysaccharide-stimulated prostaglandin E(2) generation, a marker of COX-2 activity ex vivo, was caused by ibuprofen (>or=80%) or celecoxib (>or=70%) but not placebo.CONCLUSIONS:
Unlike ibuprofen, celecoxib did not interfere with the inhibition of platelet COX-1 activity and function by aspirin despite a comparable suppression of COX-2 ex vivo in patients with osteoarthritis and stable ischemic heart disease.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Pirazóis
/
Sulfonamidas
/
Aspirina
/
Ibuprofeno
/
Isquemia Miocárdica
Tipo de estudo:
Clinical_trials
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Itália