GASTROINTESTINAL IRRITANCY, ANTIINFLAMMATORY ACTIVITY, AND PROSTANOIDINHIBITION IN THE RAT - DIFFERENTIATION OF EFFECTS BETWEEN NABUMETONEAND ETODOLAC

Many nonsteroidal antiinflammatory drugs have the ability to cause gas trointestinal damage in both animals and man. The aim of the present s tudy was to compare nabumetone, a nonacidic drug, with etodolac on rat gastric mucosal damage and prostanoid synthesis, while concurrently m easuring prostanoid production during edema formation in a carrageenan model of paw inflammation. The results showed that both drugs inhibit ed paw exudate prostaglandin E2 and edema significantly, but they did wt inhibit gastric prostanoid production 4 hr after dosing. Gastric da mage, however, was observed with etodolac. Additional time-course stud ies showed that over a 4-hr period, etodolac, unlike nabumetone, marke dly inhibited gastric mucosal prostaglandin E2 production, which was a ssociated with gastric erosion formation. Further studies demonstrated that nabumetone did not induce gastrointestinal damage or blood loss when administered to rats in a high antiinflammatory oral dose. In con trast, etodolac produced marked gastrointestinal damage and bleeding, which was evident for up to 48 hr after the dose. It is suggested that nabumetone's favorable gastrointestinal irritancy profile may relate, in part, to its nonacidic nature and to its differential effects on p rostanoid production.