ANTACIDS IN EXPERIMENTAL GASTRIC-ULCER HEALING - PHARMACOKINETICS OF ALUMINUM AND QUALITY OF HEALING

Objective: We studied the adherence of aluminium to ulcerated mucosa and the quality of ulcer healing during treatment with aluminium-containing topical anti-ulcer drugs. Methods: Aluminium concentrations in ulcerated and non-ulcerated gastric mucosa were assessed in 80 rats with cryo-ulcers treated for 2 days with the antacid hydrotalcite, sucralfate or placebo. The diameter of ulcers and the mucosal height in ulcer margins and scars were measured histologically in an additional 64 rats with cryo-ulcers treated for 8 and 15 days with placebo, antacid, omeprazole or antacid + omeprazole. Results: The aluminium concentration-time curve showed a rapid decrease in aluminium in non-ulcerated mucosa and gastric juice in antacid-treated rats. By 1, 4, 8 and 24 h after antacid administration, the aluminium concentration was increased in ulcerated mucosa compared to non-ulcerated mucosa by 1.0-, 3.9-, 5.4- and 3.3-fold, respectively. By 8 h after sucralfate administration, this ratio was 5.2. Compared to placebo, the height of the mucosal margin (day 8) and scar (day 15) was significantly increased in antacid- and significantly decreased in omeprazole- and antacid + omeprazole-treated rats. Conclusion: Adherence of aluminium to ulcerated mucosa may contribute to the anti-ulcer activity of antacid and sucralfate. The antacid hydrotalcite provides better restoration of glandular structure in the ulcer scar than omeprazole; this advantage is lost by cotreatment with omeprazole.