The anti-inflammatory drug nabumetone lacks the gastrointestinal damaging potential of loxoprofen or naproxen.

The effects of nabumetone, naproxen or loxoprofen were examined for anti-inflammatory activity and for effects on gastric mucosal integrity in a rat model of carrageenan-induced paw oedema. All three compounds produced effective anti-inflammatory activity which was associated with dose-related reductions in PGE2 concentration of the inflammatory exudate. However, naproxen and loxoprofen markedly inhibited gastric mucosal 6-keto-PGF1α, production which was accompanied by increases in gastric erosion formation. In contrast, nabumetone inhibited gastric mucosal 6-keto-PGF1α production by only 47% and did not induce gastric damage.In experiments designed to detect gastric and intestinal irritancy, nabumetone, naproxen or loxoprofen were administered orally in single high anti-inflammatory doses. At 6, 24 or 48 hr after dosing, none of the three drugs had caused gastric damage but loxoprofen induced significant ileal damage over the course of the experiment. Associated with loxoprofen-induced ileal damage was a significant increase in myeloperoxidase activity of the ileal tissue 6 hr after dosing, indicating that an inflammatory reaction either precedes or accompanies such damage. Gastrointestinal blood loss was unaltered by any of the drugs over a period of 48 hr. In a cold-restraint rat model of gastric damage where mucosal integrity is compromised, nabumetone failed to increase existing gastric damage whereas both naproxen and loxoprofen increased damage signifcantly. The present study shows that nabumetone, unlike naproxen or loxoprofen, does not cause gastrointestinal irritancy in this species when administered in a high anti-inflammatory dose.