Effect of 7-day therapy with different doses of the proton pump inhibitor lansoprazole on the intragastric pH in healthy human subjects

Background: Systematic, randomized, and controlled studies on the effect of low to high doses of the proton pump inhibitor lansoprazole on intragastri c acidity and plasma gastrin levels have not previously been performed. Met hods: We investigated the effect of 7-day therapy with different doses of l ansoprazole (15 mg once or twice daily, 30 mg once or twice daily, and 15 m g three times daily) on intragastric acidity and meal-stimulated daytime pl asma gastrin levels in 12 healthy Helicobacter pylori-negative human subjec ts in a randomized, double-blind, placebo-controlled, 6-way crossover study . On days 1, 2, and 7 of the study 24-h intragastric ps-metry and 12-h inte grated daytime plasma gastrin determinations were done. Results: Lansoprazo le in a dose regimen of 1 x 30 mg/day, 3 x 15 mg/daily, and 2 x 30 mg/day s ignificantly (P < 0.05) increased the intragastric 24-h median pH on days 1 , 2, and 7 of therapy as compared with placebo. Lansoprazole in doses of 1 x 15 mg/day and 2 x 15 mg/day significantly increased the intragastric 24-h median pH on days 2 and 7 but not on day 1 of therapy. Doses of 3 x 15 mg and 2 x 30 mg lansoprazole daily significantly increased the intragastric 2 4-h median pH on days 2 and 7 of treatment as compared with 1 x 30mg lansop razole daily. Except for 1 x 15 mg lansoprazole on day 1 of therapy, all gi ven dose regimens of lansoprazole (15-60 mg/day) significantly (P < 0.05) s timulated the 12-h integrated meal-stimulated daytime plasma gastrin respon se (pM x min) on days 1, 2, and 7 of therapy as compared with placebo. Conc lusion: A dose of 1 x 30 mg/day is nearly as potent as higher dose regimens of lansoprazole. Thus it most Likely is the optimum dose for therapy of ga stric and duodenal peptic lesions. A dose of 1 x 15 mg lansoprazole daily i s a potent inhibitor of gastric acid output and could be a therapeutic dose for prevention of peptic lesions (that is, reflux oesophagitis or ulcers).