Gastric mucosal adaptation to etodolac and naproxen.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently cause damage to the gastroduodenal mucosa, principally by suppressing mucosal prostaglandin synthesis. However, such acute mucosal injury usually resolves, despite continued NSAID administration, by a process known as adaptation. Newer NSAIDs, such as etodolac, have been developed to minimize effects on prostaglandin synthesis.


OBJECTIVE
To determine whether 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 etodolac 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 gastric damage (median grade and interquartile range, IQR) occurred during the first 24 h of administration, being greater with naproxen (2.0, IQR 1.0-3.0) than etodolac (1.0, IQR 1.0-1.5; P = 0.03). Such damage was associated with a fall in antral blood flow in the naproxen group (mean +/- 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 group from 43.5 +/- 2.24 to 49.5 +/- 3.6 arbitrary units. With continued intake this damage resolved in all subjects taking etodolac and in eight of 14 subjects on naproxen. Resolution in the naproxen group was associated with a return to normal of antral blood flow.


CONCLUSIONS
These observations suggest that etodolac causes less mucosal damage than naproxen and that adaptation occurs to both.
Lipscomb
G R
GR
Department of Gastroenterology, Salford Hospitals NHS Trust, Manchester, UK.
Wallis
N
N
Armstrong
G
G
Goodman
M J
MJ
Rees
W D
WD
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D004386:Duodenum / Q000187:drug effects; D004724:Endoscopy; D017308:Etodolac / Q000009:adverse effects* / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017308:Etodolac; D009288:Naproxen