INFLUENCE OF FASTING AND CIMETIDINE ON THE RELATIONSHIP BETWEEN ULCEROGENIC AND ANTI‐INFLAMMATORY PROPERTIES OF INDOMETHACIN

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Abstract
1 Further studies have been carried out on the relationship between ulcerogenic and anti-inflammatory properties of indomethacin in the rat. 2 Fasting, which increases gastric and reduces intestinal lesions, enhances the anti-oedema properties of indomethacin. 3 The presence of intestinal lesions, greatly increases the anti-oedema properties of indomethacin through a mechanism(s) unrelated to the specific pharmacological properties of this drug. 4 Studies with cimetidine, have shown that the enhancement of anti-oedema effects produced by fasting are due to specific pharmacological properties of indomethacin rather than to non specific effects related to the presence of gastric ulcers. 5 The greater anti-inflammatory effects of indomethacin in fasted as compared to fed animals must be attributed to the greater amount of indomethacin available for tissue distribution rather than other mechanisms associated with free fatty acid mobilization. 6 In view of ineffectiveness in preventing intestinal lesions, the use of cimetidine for prevention or reduction of indomethacin-induced gastrointestinal disturbances in humans is contraindicated.