Dog and Swine as Models for Testing Indomethacin Induced Gastrointestinal Irritation

Abstract

Indomethacin is a popular anti-inflammatory agent. One of its side-effects is gastrointestinal irritation. For the development of less irritating drug formulations it is useful to have a suitable animal model. The aim of the present study was to test the domestic swine (Yorkshire) and beagle dog for this purpose. According to previous studies the alimentary canal of the omnivorous swine may resemble human more than that of the beagle dog (Mount and Ingram 1971).

The animals were administered various doses and formulations of indomethacin every 12 h for several days. Gastrointestinal symptoms were observed carefully during this period. At necropsy, attention was focused on the gastrointestinal tract.

In the pigs the histopathological observations were scarce. Only one animal out of ten suffered from inflammation of the colon and gastrointestinal bleeding. Two more pigs showed moderate proctitis.

The dogs were more sensitive than the pigs. In the dog also the irritation potential of various formulas was easier to calculate. At the same dose level as the swines five animals out of six suffered from moderate or severe gastrointestinal involvement.

It is concluded that the beagle dog responds more easily to gastrointestinal irritation than the swine. The dog’s gastrointestinal tract is also sensitive enough to show differences in responses to various drug formulations. The reason for the sensitivity probably is the extensive enterohepatic circulation of indomethacin in the dog (Teelman 1983). Therefore, the sensitivity of the dog may be too excessive to give predictable results for use in man.