Nabumetone, an effective anti-inflammatory agent, lacks gastrointestinal irritancy in the rat when dosed orally for one month: comparison with tiaprofenic acid and etodolac.
OBJECTIVE
To determine the effects of nabumetone, compared with tiaprofenic acid and etodolac, on anti-inflammatory efficacy and gastrointestinal irritancy in the rat when dosed orally for one month at a high anti-inflammatory dose.


METHODS
Carrageenan paw edema was used as a model of inflammation. Gastrointestinal mucosal integrity was assessed by concurrently measuring ulcer formation. mucosal and tissue prostanoid production and plasma haptoglobin. Haemoglobin, present in the cecal contents, was used as a measure of blood loss.


RESULTS
Nabumetone, tiaprofenic acid and etodolac inhibited inflammation. Etodolac induced marked gastrointestinal damage and blood loss whereas tiaprofenic acid caused only gastric damage. Nabumetone was found not to alter mucosal integrity.


CONCLUSIONS
Nabumetone proved to be an effective anti-inflammatory agent that was devoid of gastrointestinal irritancy.
Melarange
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R
SmithKline Beecham Pharmaceuticals, Research and Development Technologies Harlow, Essex, UK.
Gentry
C
C
Blower
P R
PR
Toseland
C D
CD
Spangler
R
R
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001835:Body Weight; D002074:Butanones / Q000008:administration & dosage / Q000009:adverse effects*; D002351:Carrageenan; D002432:Cecum / Q000737:chemistry; D004064:Digestive System / Q000187:drug effects*; D017308:Etodolac / Q000008:administration & dosage / Q000009:adverse effects*; D005122:Exudates and Transudates / Q000737:chemistry; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D006242:Haptoglobins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D007082:Ileum / Q000187:drug effects; D008297:Male; D000077430:Nabumetone; D011422:Propionates / Q000008:administration & dosage / Q000009:adverse effects*; D011453:Prostaglandins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014456:Ulcer / Q000209:etiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D006242:Haptoglobins; D006454:Hemoglobins; D011422:Propionates; D011453:Prostaglandins; C021270:tiaprofenic acid; D017308:Etodolac; D002351:Carrageenan; D000077430:Nabumetone