Effects of nonsteroidal, antiinflammatory drugs on gastrointestinal injury and prostanoid generation in healthy volunteers.
A new nonsteroidal, antiinflammatory drug, carprofen, was compared with indomethacin as to their effects on mucosal injury and prostanoid biosynthesis. A prospective, double-blind endoscopy study was performed in 40 healthy adults. After baseline normal endoscopy, 20 subjects were randomly assigned to either indomethacin (25 mg four times daily) or carprofen (150 mg twice daily) for eight days and re-endoscoped. Urinary and gastric mucosal prostaglandin generation, respectively, of PGE2 and PGF2 alpha, and PGE and 6-keto-PGF1 alpha was determined. Minor subjective symptoms occurred in six of 20 indomethacin (including four of eight with gastrointestinal injury) and in three of 20 carprofen subjects. Indomethacin and carprofen reduced gastric and urinary prostaglandin synthesis to a similar degree. Gastrointestinal injury was present in eight of 20 indomethacin and in none of 20 carprofen subjects. This study fails to establish a relationship between duodenal mucosal lesions and gastric prostanoid generation and confirms the lack of correlation between indomethacin-induced duodenal injury and subjective symptomatology. Carprofen appears to produce less objective damage in the upper gastrointestinal tract than indomethacin at comparable clinical doses.
Levine
R A
RA
Department of Medicine, State University of New York Health Science Center, Syracuse.
Petokas
S
S
Nandi
J
J
Enthoven
D
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002227:Carbazoles / Q000009:adverse effects; D004064:Digestive System / Q000187:drug effects*; D004311:Double-Blind Method; D004341:Drug Evaluation; D004724:Endoscopy; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects; D011446:Prospective Studies; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis*; D011863:Radioimmunoassay; D012016:Reference Values; D013607:Tablets
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D011453:Prostaglandins; D013607:Tablets; C007005:carprofen; D007213:Indomethacin