GASTRIC-MUCOSAL ADAPTATION TO ETODOLAC AND NAPROXEN

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently c ause damage to the gastroduodenal mucosa, principally by suppressing m ucosal prostaglandin synthesis. However, such acute mucosal injury usu ally resolves, despite continued NSAID administration, by a process kn own as adaptation. Newer NSAIDs, such as etodolac, have been developed to minimize effects on prostaglandin synthesis, Aim: To determine whe ther etodolac causes less acute damage than naproxen, and whether the damage produced resolves with continued NSAID administration. Methods: Twenty-four healthy volunteers were given a 28-day course of either e todolac 300 mg b,d, or naproxen 500 mg b,d, Gastroduodenal damage was assessed using a modified Lanza scoring system and mucosal blood flow with laser doppler flowmetry at endoscopy before NSAID administration and during days 1, 7 and 28 of continued intake. Results: Maximum gast ric damage (median grade and interquartile range, IQR) occurred during the first 24 h of administration, being greater with naproxen (2.0, I QR 1.0-3.0) than etodolac (1.0, IQR 1.0-1.5; P = 0.03). Such damage wa s associated with a fall in antral blood now in the naproxen group (me an +/- S.E.M.) from 54.5 +/- 3.4 to 43.8 +/- 3.4 arbitrary units (P = 0.07) and a slight increase in mucosal blood flow in the etodolac grou p from 43.5 +/- 2.24 to 49.5 +/- 3.6 arbitrary units. With continued i ntake this damage resolved in all subjects taking etodolac and in eigh t of 14 subjects on naproxen. Resolution in the naproxen group was ass ociated with a return to normal of antral blood flow. Conclusions: The se observations suggest that etodolac causes less mucosal damage than naproxen and that adaptation occurs to both.