Species Differences in Susceptibility to the Gastro-Ulcerogenic Action of Anti-Inflammatory Agents

(1) In the different vertebrates studied (mammals, amphibians, birds and fish) phenylbutazone, which was selected as a representative anti-inflammatory agent, was found to exert a varying degree of gastroulcerogenic activity. (2) The four anti-inflammatory agents, phenyl-butazone, oxyphenbutazone, indomethacin and flufenamic acid displayed a potent, acute ulcerogenic effect when administered orally to the rat. In the guinea pig and the mouse, a similar effect was only observed in response to higher (in some cases considerably higher) doses. (3) The margin between the median ulcerogenic and median lethal doses of phenylbutazone, oxyphenbutazone and flufenamic acid was narrow in the guinea pig and the mouse, but wide in the rat. In the case of indomethacin, it was wide in the mouse and narrow in the other two species. (4) The anti-inflammatory activity of the four preparations against acute oedema in the same species differed. (5) In the guinea pig, all four preparations showed a favourable therapeutic ratio, i.e. relation between anti-inflammatory and ulcerogenic activity; in the mouse and the rat, no consistent relationship was demonstrable. The most important finding emerging from these experiments is that ulcerogenicity and anti-inflammatory potency – in terms of the doses required to elicit these effects -need not necessarily parallel each other.