Gastric bleeding and gastric secretion with sulindac and naproxen

We have examined concurrent gastric secretory rates and bleeding by a gastric wash technique during treatment with naproxen, sulindac, and placebo. Twelve subjects, in each of 4 treatment periods, took either placebo, sulindac 200 mg, naproxen 250 mg, or naproxen 375 mg, twice a day for four days. Of the resultant 192 days (12 subjects, 4 drugs, 4 days/drug), two thirds of all days showed bleeding at a rate less than 0.5 ml/day; this low rate of bleeding was seen with all treatments. In spite of this minor bleeding, we were able to show statistically significantly less bleeding with placebo than with drugs; placebo never resulted in a maximum rate of bleeding for any subject. Distinctions between drugs on the basis of bleeding, however, were not possible. Correlations between outputs of acid and chloride were not significantly affected by any of these drugs. In contrast to previous results with aspirin, no correlation between rates of bleeding and gastric secretion could be established. The low water solubility of these drugs at the pH of gastric contents may account for their causing very little bleeding. In effect, the greater the gastric secretion of acid the less the absorption through the gastric mucosa.