THE INFLUENCE OF AGE, GENDER, HELICOBACTER-PYLORI AND SMOKING ON GASTRIC-MUCOSAL ADAPTATION TO NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Introduction: Oral NSAIDs cause acute gastric injury that resolves, de spite continued administration, by a process known as adaptation. Litt le is known about the factors that influence this process. Methods: Si xty-two healthy volunteers were given a 28-day course of either etodol ac 300 mg b.d. (13 subjects), naproxen 500 mg b.d. (23), enteric-coate d diclofenac (10) or effervescent diclofenac 50 mg b.d. (16). All subj ects were gastroscoped before and on days 1, 7 and 28 during drug admi nistration, to assess gastric mucosal damage using a modified Lanza sc ale. Subjects were then divided into three categories: those who adapt ed 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 w hom 42 adapted completely, 13 adapted incompletely and four showed no evidence of adaptation. The mean age of subjects was lower in those wh o 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 pears, P = 0.01). There was no evidence of gender influencing adaptation. Of 1 7 H. pylori-positive subjects, a higher proportion had incomplete adap tation, with only nine subjects adapting completely (53% vs. 81%, P = 0.04). Sixteen subjects were smokers, of whom a greater proportion sho wed no evidence of adaptation (19% vs. 2%, P = 0.03). A smaller propor tion of those who took naproxen (48%) adapted completely than those wh o took enteric-coated diclofenac (89%), effervescent diclofenac (75%) or etodolac (91%, P = 0.03). Conclusion: Some adaptation occurred in o ver 90% of subjects after 4 weeks dosing with an NSAID, but adaptation was less frequent in older subjects and in smokers. Complete adaptati on occurred less frequently in H. pylori-positive subjects and in thos e who were given naproxen.