title: Recent insight into the mechanism of gastrointestinal tract ulceration.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their gastrotoxic and duodenotoxic effects. A few years ago the introduction of a sustained release form of indomethacin led to an apparently high incidence of jejunal and ileal perforations. Recently, Langman in England was able to demonstrate that the intake of some NSAIDs is related to an enhanced incidence of ileal and jejunal perforations in rats and dogs, even after parenteral or rectal administration. We have been able to show that: 1. There is a correlation between biliary excretion of NSAIDs or ester conjugates of these drugs and ileal perforations in rats. 2. In contrast to dogs there is no (ibuprofen) or little enterohepatic circulation (diclofenac and diflunisal) in man. This agrees with the low incidence of ileal and jejunal ulcers reported with these drugs in contrast to indomethacin or piroxicam. 3. Reduction of enterohepatic circulation of indomethacin in rats by dietary means reduces the degree of small intestinal erosions and ulcerations in parallel with the reduced biliary excretion of the drug. It may be safely assumed that the enterohepatic circulation of some NSAIDs, particularly indomethacin and piroxicam, may contribute to the reported incidence of ileal and jejunal damage caused by these drugs. These drugs may, on the other hand, have clear-cut advantages as well.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Erlangen-Nürnberg, Federal Republic of Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brune
authors.forename: K
authors.initials: K
authors.lastname: Dietzel
authors.forename: B
authors.initials: B
authors.lastname: Nürnberg
authors.forename: H T
authors.initials: HT
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000378:metabolism; D004764:Enterohepatic Circulation; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced*; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced*; D011448:Prostaglandin Antagonists / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011448:Prostaglandin Antagonists