The influence of age, gender, Helicobacter pylori and smoking on gastric mucosal adaptation to non-steroidal anti-inflammatory drugs.
BACKGROUND
Oral NSAIDs cause acute gastric injury that resolves, despite continued administration, by a process known as adaptation. Little is known about the factors that influence this process.


METHODS
Sixty-two healthy volunteers were given a 28-day course of either etodolac 300 mg b.d. (13 subjects), naproxen 500 mg b.d. (23), enteric-coated diclofenac (10) or effervescent diclofenac 50 mg b.d. (16). All subjects were gastroscoped before and on days 1, 7 and 28 during drug administration, to assess gastric mucosal damage using a modified Lanza scale. Subjects were then divided into three categories: those who adapted completely, those who adapted incompletely and those who showed no adaptation. The proportion of subjects in each group was compared with respect to age, gender, smoking, the presence of Helicobacter pylori, and the NSAID prescribed.


RESULTS
Fifty-nine subjects (median age 25.0 years, range 18-70) developed initial gastric injury to NSAIDs of whom 42 adapted completely, 13 adapted incompletely and four showed no evidence of adaptation. The mean age of subjects was lower in those who adapted (26.8 +/- 9.8 years) than those who adapted incompletely (32.5 +/- 10.3 years) and those who did not adapt (42.0 +/- 15.7 years, P = 0.01). There was no evidence of gender influencing adaptation. Of 17 H. pylori-positive subjects, a higher proportion had incomplete adaptation, with only nine subjects adapting completely (53% vs. 81%, P = 0.04). Sixteen subjects were smokers, of whom a greater proportion showed no evidence of adaptation (19% vs. 2%, P = 0.03). A smaller proportion of those who took naproxen (48%) adapted completely than those who took enteric-coated diclofenac (89%), effervescent diclofenac (75%) or etodolac (91%, P = 0.03).


CONCLUSIONS
Some adaptation occurred in over 90% of subjects after 4 weeks dosing with an NSAID, but adaptation was less frequent in older subjects and in smokers. Complete adaptation occurred less frequently in H. pylori-positive subjects and in those who were given naproxen.
Lipscomb
G R
GR
Department of Gastroenterology, Manchester Royal Infirmary, UK.
Campbell
F
F
Rees
W D
WD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D004361:Drug Tolerance; D017308:Etodolac / Q000009:adverse effects*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D012189:Retrospective Studies; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013272:Stomach Diseases / Q000139:chemically induced* / Q000209:etiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D017308:Etodolac; D009288:Naproxen