Effect of carprofen and indomethacin on gastric function, mucosal integrity and generation of prostaglandins in men.
The effects of indomethacin and carprofen on gastric secretion, serum gastrin level, electropotential difference, gastric microbleeding, DNA loss, mucosal blood flow and the production of mucosal prostaglandins (PGs) were investigated in a double-blind cross-over study in 18 healthy volunteers after one week of treatment. We did not observe any significant changes in basal and pentagastrin-stimulated gastric secretory parameters, serum gastrin level and electro-potential difference before and after treatment with these drugs. Mucosal blood flow was significantly reduced following indomethacin treatment. The most pronounced differences were found in endoscopic score studies of gastric mucosa. After indomethacin all subjects developed multiple erosions, submucosal haemorrhages, and half of them showed diffuse antral erythema. These effects were accompanied by a significant increase in both gastric microbleeding and DNA loss, and significant decrease in the production of PGE2. We concluded that carprofen, in contrast to indomethacin, did not alter gastric mucosal integrity and production of PGE2. This study indicates that the gastric mucosal damage by non-steroid anti-inflammatory compounds (NOSAC) depends upon the suppression of PGE2 biosynthesis, and that endogenous PGE2 is involved in the control of mucosal blood flow and mucosal integrity.
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001775:Blood Circulation; D002227:Carbazoles / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015232:Dinoprostone; D004311:Double-Blind Method; D004724:Endoscopy; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000097:blood; D006471:Gastrointestinal Hemorrhage / Q000503:physiopathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis*; D013270:Stomach / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D002227:Carbazoles; D005755:Gastrins; D011458:Prostaglandins E; C007005:carprofen; D015232:Dinoprostone; D007213:Indomethacin