GASTRIC-MUCOSAL INJURY AND ADAPTATION TO ORAL AND RECTAL ADMINISTRATION OF NAPROXEN

Introduction: 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 uncerta in. Methods: Twenty-four healthy volunteers were allocated either oral or rectal naproxen 500 mg b.d, and gastroscoped before and during day s 1, 7 and 28 of dosing, Macroscopic gastric damage was assessed using a modified Lanza score, mucosal blood now recorded using laser Dopple r flowmetry and prostaglandin E(2) (PGE(2)) measured in antral mucosal biopsies. Results: Maximal gastric damage occurred during the first 2 4 h in the oral naproxen group and was associated with a fall in antra l 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 o ral naproxen, gastric damage resolved and antral mucosal blood now ret urned to baseline (54.2 +/- 3.7 a.u.). No macroscopic damage or signif icant changes in mucosal blood low were observed during rectal adminis tration. There was no significant difference between mucosal PGE, conc entrations 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) i n those receiving oral naproxen and from 235 +/- 55 to 107 +/- 31 pg/m g at day 1 (P = 0.1) in those receiving rectal naproxen, and remaining suppressed throughout the study in both groups. Conclusions: These ob servations suggest that acute mucosal damage and changes in mucosal da mage and changes in mucosal blood flow are caused by the topical rathe r than systemic actions of naproxen.