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Gastric mucosal injury and adaptation to oral and rectal administration of naproxen
Author(s) -
LIPSCOMB G. R.,
REES W. D. W.
Publication year - 1996
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1996.726118000.x
Subject(s) - medicine , naproxen , oral administration , gastroenterology , blood flow , rectal administration , antrum , stomach , pathology , alternative medicine
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 E 2 (PGE 2 ) 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 PGE 2 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.