Gastric mucosal injury and adaptation to oral and rectal administration of naproxen.
BACKGROUND
Oral nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute gastric mucosal injury but the relative importance of systemic and topical effect of NSAIDs to overall gastric damage remains uncertain.


METHODS
Twenty-four healthy volunteers were allocated either oral or rectal naproxen 500 mg b.d. and gastroscoped before and during days 1, 7 and 28 of dosing. Macroscopic gastric damage was assessed using a modified Lanza score, mucosal blood flow recorded using laser Doppler flowmetry and prostaglandin E2 (PGE2) measured in antral mucosal biopsies.


RESULTS
Maximal gastric damage occurred during the first 24 h in the oral naproxen group and was associated with a fall in antral mucosal blood flow (mean +/- S.E.M.) from 58.2 +/- 3.3 to 46.6 +/- 4.1 arbitrary units (a.u.) (P < 0.05). With continued administration of oral naproxen, gastric damage resolved and antral mucosal blood flow returned to baseline (54.2 +/- 3.7 a.u.). No macroscopic damage or significant changes in mucosal blood flow were observed during rectal administration. There was no significant difference between mucosal PGE2 concentrations in those receiving oral or rectal naproxen, falling from an initial level of 335 +/- 29 to 155 +/- 49 pg/mg at day 1 (P = 0.06) in those receiving oral naproxen and from 235 +/- 55 to 107 +/- 31 pg/mg at day 1 (P = 0.1) in those receiving rectal naproxen, and remaining suppressed throughout the study in both groups.


CONCLUSIONS
These observations suggest that acute mucosal damage and changes in mucosal blood flow are caused by the topical rather than systemic actions of naproxen.
Lipscomb
G R
GR
Salford Royal Hospitals NHS Trust, University of Manchester School of Medicine, UK.
Rees
W D
WD
D000284:Administration, Oral; D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects; D010120:Oxytocics / Q000032:analysis; D011446:Prospective Studies
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010120:Oxytocics; D009288:Naproxen; D015232:Dinoprostone