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AB0029 Selective inhibition of cox-2 on acid-induced gastric ulcers: comparison of meloxicam, piroxicam and nimesulide
  1. H Schierok,
  2. I Erni,
  3. S Schlager,
  4. B Guth,
  5. M Pairet
  1. General Pharmacology, Boehringer Ingelheim Pharma KG, Biberach, Germany

Abstract

Background Non-steroidal anti-inflammatory drugs are known to have adverse effects on the gastro-intestinal system through the inhibition of prostaglandin synthesis by cyclooxygenase-1 (COX-1). Reducing inflammation by selectively inhibiting COX-2 has reduced gastrointestinal side effects. The effect of selective COX-2 inhibition or non-selective inhibition on the aggravation of gastric lesions due to other causes, however, has not been thoroughly examined.

Objectives We tested the hypothesis that agents that selectively inhibit COX-2 (meloxicam and nimesulide) would aggravate HCL-induced gastric lesions in rats less than a nonselective inhibition (piroxicam).

Methods Gastric lesions were induced in male rats (N = 10 per group) using 0.45 N HCL. The test drug (1.5 or 3 mg/kg) was administered s.c. 60 min before the instillation of HCL (1 ml/100 g BW) into the stomach. One hour later the animals were euthanized and the stomachs were removed, rinsed, opened along the greater curvature and photographed. Lesions were quantified in the fundus region using computer-assisted planimetry of the digital images.

Results The stomach area of all groups was comparable. The results in terms of absolute ulcer area, ratio of ulcer area to total fundus area and this ratio as compared to the control group is summarised in the following Table 1.

Abstract AB0029 Table 1

Conclusion This in vivo test supports the hypothesis that selective inhibition of COX-2 has less effect on acid-induced gastric ulcers in rats than a nonselective inhibition. In this test meloxicam had no effect on gastric lesions, nimesulide only a trend for ulcer enhancement but piroxicam produced a clear augmentation of HCL-induced gastric lesions.

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