Duration of effect of lansoprazole on gastric pH and acid secretion in normal male volunteers.

AIM: A double-blind, placebo-controlled study to assess the duration of effect of lansoprazole 30 mg o.m. on intragastric pH, acid secretion, gastrin levels, the potential for rebound acidity, and the relationship between gastric acid and drug pharmacokinetic parameters. METHODS: Sixteen subjects were treated with lansoprazole 30 mg daily or placebo for 14 days, followed by a 7-day post-dosing period and a post-study evaluation on day 28. Ambulatory 24-h pH was recorded and pentagastrin-stimulated acid secretion measured. Plasma kinetics of lansoprazole were determined. RESULTS: Mean intragastric pH in the lansoprazole group increased significantly (P < 0.05) from baseline to day 14 compared to placebo. After cessation of treatment, secretory activity, as measured by intragastric pH, basal acid output and stimulated acid output, returned to baseline in 2 to 4 days without any overshoot, indicating the absence of acid rebound. Lansoprazole's terminal disposition half-life was 1.11 h. Mean pH and serum gastrin returned to baseline with half-lives of 22 and 19 h, respectively. CONCLUSIONS: Lansoprazole 30 mg daily significantly increases mean intragastric pH without producing acid rebound. Regeneration of acid production depends primarily on de novo synthesis of the acid pump.

Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis.

BACKGROUND: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastro-oesophageal reflux disease (GERD). METHODS: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. RESULTS: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night-time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. CONCLUSIONS: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD.

Dose-response relationship of lansoprazole to gastric acid antisecretory effects.

BACKGROUND: Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro-oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment. OBJECTIVE: To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects. METHODS: Intragastric 24-h pH monitoring was performed in 32 healthy subjects in a randomized, double-blind, four-way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days. RESULTS: Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple-dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple-dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post-regimen serum gastrin values increased by 50-130% from pre-study mean values but remained within normal range and returned to pre-study values 7-14 days post-dosing. CONCLUSIONS: Multiple-dose regimens of lansoprazole (> or =30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.

A placebo-controlled dose-ranging study of lansoprazole in the management of reflux esophagitis.

OBJECTIVE: We compared the efficacy of three different doses of the proton pump inhibitor lansoprazole in the management of reflux esophagitis. METHODS: Two hundred ninety-two patients with endoscopically confirmed reflux esophagitis were enrolled in a double-blind, multicenter study and were randomized to lansoprazole 15, 30, or 60 mg or placebo administered once daily for 8 wk. RESULTS: Healing rates after 4 wk of lansoprazole 15, 30, and 60 mg/d were 67.6%, 81.3%, and 80.6%, respectively. These were all significantly superior (p < 0.001) to placebo, which produced endoscopic healing in only 32.8% of the patients after 4 wk. The 4-wk healing rates with lansoprazole 30 or 60 mg were significantly higher than that with lansoprazole 15 mg (p < 0.05), confirming a dose-response effect. Cumulative healing rates after 8 wk of treatment were 52.5% with placebo and 90.0%, 95.4%, and 94.4% with lansoprazole 15, 30, and 60 mg, respectively (p < 0.001 for all doses of lansoprazole vs placebo). Lansoprazole was also significantly superior to placebo in relieving symptoms in patients with reflux esophagitis. Lansoprazole was well tolerated, and no serious treatment-related adverse events were encountered. Up to 3 months after discontinuation of treatment, all lansoprazole-treated groups had more patients free of endoscopic evidence of esophagitis than the group treated with placebo. CONCLUSIONS: Lansoprazole was safe and effective for the treatment of reflux esophagitis in this trial. This study indicates that the optimum daily dose of lansoprazole for reflux esophagitis is 30 mg.

The comparative effects of lansoprazole, omeprazole, and ranitidine in suppressing gastric acid secretion.

The effects on 24-hour intragastric pH levels of once-daily doses of lansoprazole 15 mg and lansoprazole 30 mg were compared with the effects of omeprazole 20 mg QD and ranitidine 150 mg QID in a phase I, randomized, double-masked, four-way crossover study conducted in 29 healthy male volunteers. Subjects received each treatment regimen for 5 consecutive days with at least a 2-week washout between treatment periods. Ambulatory 24-hour intragastric pH values were monitored in each subject at baseline (2 days before crossover period 1) and again before dosing on day 5 of each of the four crossover treatment periods. Gastric pH values increased during all four regimens, with significantly higher mean 24-hour pH values noted in subjects receiving lansoprazole 30 mg QD (4.53 +/- 0.16) compared with those receiving lansoprazole 15 mg QD (3.97 +/- 0.16), omeprazole 20 mg QD (4.02 +/- 0.16), or ranitidine 150 mg QID (3.59 +/- 0.16). Lansoprazole 30 mg produced significantly greater mean percentages of time that the gastric pH was above 3.0 and 4.0 (75% and 63%, respectively) compared with the other treatment regimens. The mean percentages of time during which gastric pH was above 3.0 and 4.0, respectively, for the other treatments were lansoprazole 15 mg, 64% and 48%; omeprazole 20 mg, 63% and 51%; and ranitidine 150 mg, 52% and 38%. All treatment regimens were well tolerated, with no clinically significant differences between the regimens. Multiple-dose lansoprazole 30 mg QD produced a significantly increased intragastric pH level and significantly longer durations of increased intragastric pH level compared with lansoprazole 15 mg QD, omeprazole 20 mg QD, and ranitidine 150 mg QID.

Prevention of duodenal ulcer recurrence with 15 mg lansoprazole: a double-blind placebo-controlled study. The Lansoprazole Study Group.

Although eradication of Helicobacter pylori cures duodenal ulcer, some patients are not infected and others are treatment failures. This randomized, double-blind, placebo-controlled study assessed the value of treatment with low-dose lansoprazole in preventing duodenal ulcer recurrence. One hundred eighty-six patients with endoscopic documentation of healed duodenal ulcer received 15 mg/day lansoprazole or placebo for 12 months or until ulcer recurred. Endoscopy results, symptom assessment, and fasting serum gastrin levels were obtained at multiple time points. Densities of E, EC, and G cells were assessed by biopsy when the ulcer recurred or at the final visit. Time to ulcer recurrence was significantly longer (P < 0.001) in the lansoprazole group (median >12 months) compared to placebo (median <3 months), and patients taking lansoprazole were asymptomatic longer (P < 0.05). Maintenance therapy with lansoprazole 15 mg/day suppresses acid and controls recurrence of duodenal ulcer disease.

A comparison of three doses of lansoprazole (15, 30 and 60 mg) and placebo in the treatment of duodenal ulcer. The Lansoprazole Study Group.

BACKGROUND: Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease. METHODS: A double-blind, multicentre study was undertaken in 296 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post-treatment. RESULTS: Four-week healing rates of 89.4%, 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1% on placebo (P < 0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 25.3% for the placebo group. No significant adverse events were documented during the period of this trial. CONCLUSION: Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.

A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis. Multicentre Investigational Group.

BACKGROUND: Lansoprazole is a new proton pump inhibitor which produces prolonged decrease of gastric acidity. The aim of this study was to compare lansoprazole to a standard dose of ranitidine in the treatment of patients with reflux oesophagitis. METHODS: Two hundred and forty-seven patients with erosive oesophagitis were randomly assigned to 8 weeks of treatment with either 30 mg lansoprazole once daily or 150 mg ranitidine twice daily. RESULTS: Two hundred and forty-two patients were included in the analysis. Lansoprazole (30 mg) daily, healed oesophagitis in 92.1% of patients after 8 weeks of treatment. This was significantly superior to 150 mg ranitidine b.d.s. which healed oesophagitis in 69.9% of patients (P < 0.001). Relief of reflux symptoms was superior with lansoprazole to that with ranitidine. Both lansoprazole and ranitidine were well tolerated with no serious drug-related adverse events noted. CONCLUSION: Lansoprazole, 30 mg once daily, is highly effective and safe in the short-term treatment of erosive oesophagitis.

Double-blind comparison of lansoprazole, ranitidine, and placebo in the treatment of acute duodenal ulcer. Lansoprazole Study Group.

OBJECTIVES: To study in a double-blind controlled manner the effects of lansoprazole 15 mg or 30 mg daily compared with ranitidine 300 mg once daily and placebo in the relieving of symptoms and healing of acute duodenal ulceration. METHODS: Two hundred eighty patients with duodenal ulcer entered in to the study from 30 centers. They were randomized in a double-blind manner into four groups with 80 patients entered into each active treatment group and 40 patients into the placebo group. Endoscopy was performed at 2- and 4-wk intervals to assess healing. Symptom relief was recorded, serum gastrin levels were measured, and gastric mucosal biopsies were obtained to evaluate for the presence of acute and chronic inflammation, the presence of neoplasia, and the extent of gastric endocrine growth at the time of endoscopy. RESULTS: After 4 wk of treatment using per protocol analysis, 19 of 40 (47.5%) patients receiving placebo had healed compared with 55 of 78 (70.5%) receiving ranitidine (p < 0.05 vs. placebo), 61 of 76 (80.3%) receiving lansoprazole 30 mg (p < 0.05 vs. placebo), and 72 of 78 (92.3%) receiving lansoprazole 15 mg (p < 0.05 vs. placebo and ranitidine). In patients with evaluable data, lansoprazole 30 mg and ranitidine produced greater relief of night-time symptoms and lansoprazole 15 mg produced greater relief of both day- and night-time symptoms than did placebo after 4 wk of treatment. Ranitidine increased fasting serum gastrin levels (22%; p < 0.05 vs. placebo), whereas both lansoprazole regimens produced more marked rises in serum gastrin (54% and 60%; p < 0.05 vs. placebo and ranitidine). Lansoprazole 15 mg and 30 mg also increased the density of antral G-cells (105.8% and 128.80%; p < 0.05 vs. baseline) and greater curvature Grimelius-positive cells (20.33% and 28.8%; p < 0.05 vs. baseline); there were no increases in the density of antral EC- or D-cells, and there was no alteration of gastric endocrine growth as judged by the Solcia classification. Both ranitidine and lansoprazole were associated with decreased antral Helicobacter pylori density accompanied, in the lansoprazole groups, by decreased antral inflammation scores. All antisecretory regimens were associated with increased inflammatory scores in the greater curvature. CONCLUSIONS: In acute duodenal ulceration, treatment with lansoprazole 15 and 30 mg produced 4-wk healing rates and symptom relief superior to those produced by placebo and the 15-mg dose similar to those produced by placebo. The 15-mg dose of lansoprazole was also superior to ranitidine in healing duodenal ulcer after 4 wk of therapy.

Treatment of reflux esophagitis resistant to H2-receptor antagonists with lansoprazole, a new H+/K(+)-ATPase inhibitor: a controlled, double-blind study. Lansoprazole Study Group.

This multicenter, randomized, double-blind, 8-wk study compared the new H+/K(+)-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to histamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine (p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine-treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.