Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen.
Aliment Pharmacol Ther
; 13(6): 761-7, 1999 Jun.
Article
em En
| MEDLINE
| ID: mdl-10383505
ABSTRACT
BACKGROUND:
Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity.AIM:
To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin.METHODS:
Healthy subjects (n = 170; age range 18-54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score >/= 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population.RESULTS:
The percentage of subjects who developed a mucosal score >/= 2 in the MK-0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated.CONCLUSIONS:
In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Úlcera Gástrica
/
Anti-Inflamatórios não Esteroides
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Aspirina
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Ibuprofeno
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Inibidores de Ciclo-Oxigenase
/
Prostaglandina-Endoperóxido Sintases
/
Úlcera Duodenal
/
Inibidores Enzimáticos
/
Isoenzimas
/
Lactonas
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Limite:
Adolescent
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Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Aliment Pharmacol Ther
Ano de publicação:
1999
Tipo de documento:
Article