Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome

BACKGROUND & AIMS: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings). METHODS: We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours. RESULTS: The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed. CONCLUSIONS: Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.     

Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome

OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.     

Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion

OBJECTIVE: Maintenance proton pump inhibitor (PPI) therapy is effective for gastric acid hypersecretory states, although data with pantoprazole are limited. The aim of this study was to evaluate the safety and efficacy of long term p.o. pantoprazole in individuals with hypersecretion. METHODS: All subjects had Zollinger-Ellison syndrome or idiopathic hypersecretion. Baseline acid output was measured in the presence of prior maintenance antisecretory therapy before pantoprazole exposure. The starting dose was 40 mg b.i.d. in most cases, and the dose was adjusted to document control within the first 2 wk of therapy. The maximal allowable dose was 240 mg daily. Acid output was measured on day 28 and then quarterly from month 3. The primary efficacy endpoint was documented control of acid secretion at 6 months, i.e., acid output in the last 1 h before the next dose of therapy of <10 mEq/h (<5 mEq/h in subjects with prior acid-reducing surgery). RESULTS: A total of 26 subjects had Zollinger-Ellison syndrome (six with multiple endocrine neoplasia syndrome type 1) and nine had idiopathic hypersecretion. Pre-enrollment therapy included omeprazole in 27 subjects and lansoprazole in eight, and 82.4% of subjects were controlled on their prior regimens. With upward dose titration, acid output was controlled in all subjects by day 10 and in all but two (6%) at the 6-month time point. Median acid secretion on therapy at 6 months was <2 mEq/h (mean 2.2 mEq/h; range 0-10.5 mEq/h) at a dose of 40 mg b.i.d. for 24 subjects, 80 mg b.i.d. for seven subjects, and 120 mg b.i.d. for two subjects. During the course of the study, five subjects required doses of 240 mg daily. Pantoprazole was generally well tolerated. No cases of anterior optic ischemic neuropathy occurred. Five subjects died during follow-up, all because of events unrelated to the study drug. CONCLUSIONS: Maintenance p.o. pantoprazole therapy at a dose of 80-240 mg/day in divided doses was both effective and generally well tolerated for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion.     

Prospective study of efficacy and safety of lansoprazole in Zollinger-Ellison syndrome

Lansoprazole, a new substituted benzimidazole H⁺, K⁺-ATPase inhibitor, profoundly inhibits gastric acid secretion and has potential use in the management of diseases such as Zollinger-Ellison syndrome (ZES). In the present study we evaluated the efficacy and safety of lansoprazole in controlling acid hypersecretion in 20 patients with ZES. The starting dose was 60 mg once daily. Control of acid hypersecretion was defined as the dose required to reduce acid secretion to <10 meq/hr in the last hour before the next dose. Doses were adjusted upwards until effective control was achieved. Patients not controlled with 120 mg once daily were placed on twice daily lansoprazole. Most patients (90%) required lansoprazole once daily. During long-term follow-up (mean 18.5 months), 25% of patients required upward dose adjustments and 25% of patients required twice daily lansoprazole. Following cessation of therapy, the mean time for gastric acid output to reach half basal acid output was 39.1 hr. Lansoprazole was well-tolerated without side effects. Clinical chemistry and hematological studies were unchanged, and no gastric carcinoids developed. These results demonstrate that lansoprazole is a safe and effective inhibitor of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Because it has a long duration of action, lansoprazole can be used to control gastric acid hypersecretion in most patients with Zollinger-Ellison syndrome using a once daily dosing schedule.     

Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients.

Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m. on ulcer healing and symptomatic relief in 219 out-patients with endoscopically assessed acute duodenal ulcer. After 2 weeks complete ulcer healing was achieved in 58%, 89% and 82% of the patients with 20 mg, 40 mg and 80 mg pantoprazole o.m., respectively. After 4 weeks, corresponding figures were 93%, 99% and 100%; the difference of the healing rates between the 20 mg and 40 mg groups at 2 weeks was statistically significant (p < 0.0001). A rapid pain relief was achieved in all treatment groups: 72% of the 20 mg group, 89% of the 40 mg group, and 84% of the 80 mg group were pain-free after 2 weeks. The difference between 20 mg and 40 mg was statistically significant (p < 0.05). Pantoprazole was well tolerated. Adverse events occurred in 13 patients; headache, skin alterations, and diarrhea were reported most frequently. Severity and frequency of adverse events did not reveal any dose-dependence. In conclusion, pantoprazole provides fast healing of acute duodenal ulcer as well as rapid improvement of ulcer symptoms. For further clinical trials in peptic ulcer disease a daily dose of pantoprazole 40 mg o.m. is recommended.     

Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose： A study on 71 patients with rheumatoid arthritis

AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This technique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.     

Effects of esomeprazole on acid output in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion

OBJECTIVES: To evaluate the efficacy and safety of oral esomeprazole in the control of gastric acid hypersecretion in patients with hypersecretory states. METHODS: In this 12-month, open-label, multicenter study, acid output (AO) was evaluated at baseline, day 10, and months 3, 6, and 12. The starting dose of esomeprazole was 40 mg or 80 mg twice daily. On day 10, patients with controlled AO were maintained on the same dose, while those with uncontrolled AO had their doses increased (maximum dose 240 mg/day) until control was attained. Esophagogastroduodenoscopy (EGD) was performed at baseline and at 6 and 12 months. Safety and tolerability were assessed throughout the study by EGD, gastric analysis, and adverse events. RESULTS: Twenty-one patients (19 with Zollinger-Ellison syndrome [ZES], 2 with idiopathic gastric acid hypersecretion [IGH]) completed the study. Of the 20 patients with controlled AO at day 10, 18 (90%) had sustained AO control for the rest of the study. At 12 months, AO was controlled in 14 of 16 patients receiving esomeprazole 40 mg twice daily, in all 4 patients receiving esomeprazole 80 mg twice daily, and in the 1 patient receiving esomeprazole 80 mg 3 times daily. At 6 and 12 months, no patient had endoscopic evidence of mucosal disease. Esomeprazole was well tolerated; 1 patient had a serious adverse event (hypomagnesemia) attributed to treatment that resolved with magnesium supplementation during continued treatment. CONCLUSION: Esomeprazole in appropriately titrated doses controls AO over 12 months in patients with hypersecretory states and is well tolerated.     

Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose: A study on 71 patients with rheumatoid arthritis

AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.     

Inhibition of Pentagastrin-Stimulated Gastric Acid Secretion by Pantoprazole and Omeprazole in Healthy Adults

Our objective was to compare the onset and duration of a single dose of pantoprazole or omeprazole on maximally stimulated gastric acid secretion. This double-blind, randomized, placebo-controlled study involved 36 healthy adults and utilized continuous pentagastrin infusion to stimulate acid secretion after administration of pantoprazole, 40 mg, omeprazole, 20 mg, or placebo. Gastric aspirates were collected over 24 hr and analyzed for volume, pH, and hydrogen ion concentration, and gastric acid outputs (GAO) were calculated. Comparison between GAO and intragastric pH was performed. Pantoprazole resulted in significantly greater inhibition of GAO than omeprazole. Mean cumulative 24-hr GAO was 164 ± 130 mEq for pantoprazole versus 283 ± 159 mEq for omeprazole (P = 0.031). Pantoprazole patients reached and maintained GAO levels below the 10-mEq/hr threshold at 5.7 hr, whereas omeprazole patients never reached this threshold. We conclude that pantoprazole significantly suppressed gastric acid secretion compared to omeprazole. Comparisons between pH and GAO showed that GAO was a more appropriate measure of gastric acid secretion than intragastric pH. This work received financial support from Wyeth Pharmaceuticals.     

Effect of Preoperative Intravenous Pantoprazole in Elective-Surgery Patients: A Pilot Study

Background This study evaluated the effects of intravenous pantoprazole on gastric volume and acid output in elective-surgical patients. Methods This is a multicenter, randomized, pilot study of adult patients receiving intravenous pantoprazole: 40 mg every 24 h, 40 mg every 12 h (q12h) or 80 mg q12h. The first dose was administered 1 h before general anesthesia for surgery. All gastric fluid was aspirated through a nasogastric tube 1 h before dosing and through the postoperative period. Aspirate volume was recorded; pH and H⁺ concentrations were measured. Result Twenty-six patients were enrolled and 21 were evaluable. Pantoprazole was well tolerated. All regimens decreased gastric acid output and volume, and increased pH within 1 h of dosing. Effects were sustained for up to 12 h following single-dose administration. Conclusions Intravenous pantoprazole administered prior to anesthesia induction may be efficacious for the reduction of gastric volume and acid output, and for pulmonary aspiration prophylaxis in surgical patients.     

Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients

BACKGROUND AND AIM: Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. METHODS: A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. RESULTS: Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. CONCLUSION: A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.     

Oral pantoprazole for erosive esophagitis: a placebo-controlled, randomized clinical trial. Pantoprazole US GERD Study Group

OBJECTIVES: The aim of this dose-response study was to compare the effectiveness of 10 mg, 20 mg, and 40 mg of pantoprazole with that of placebo tablets in the healing and symptom relief of gastroesophageal reflux disease associated with erosive esophagitis, and to determine the optimal dose. METHODS: A total of 603 patients with endoscopically confirmed (Hetzel-Dent scale) erosive esophagitis of grade 2 (64.5%) or grades 3 or 4 (35.3%) were enrolled in a double-blind, multicenter study and randomly assigned to receive pantoprazole (10 mg, 20 mg, or 40 mg) or placebo, administered once daily in the morning, for 4 or 8 wk depending on healing. RESULTS: The healing rates after 4 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 14%, 42%, 55%, and 72%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). Cumulative healing rates after 8 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 33%, 59%, 78%, and 88%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). The 40-mg pantoprazole dose produced greater rates of healing and earlier healing of esophagitis than either the 10- or 20-mg dose, regardless of severity. Pantoprazole, at any dose, was significantly more effective than placebo in relieving reflux symptoms. Patients on pantoprazole 40 mg experienced relief of symptoms on day 1 of treatment. No serious treatment-related adverse events occurred. CONCLUSIONS: Pantoprazole was safe and effective for healing erosive esophagitis and provided rapid symptomatic relief. These results indicate that pantoprazole offers a new option for treatment of erosive esophagitis. Among the three doses studied, the 40-mg dose was the most effective.     

40 mg pantoprazole and 40 mg esomeprazole are equivalent in the healing of esophageal lesions and relief from gastroesophageal reflux disease-related symptoms

BACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.     

Gastric secretion in Zollinger-Ellison syndrome. Correlation with clinical expression, tumor extent and role in diagnosis--a prospective NIH study of 235 patients and a review of 984 cases in the literature

We prospectively studied 235 patients with Zollinger-Ellison syndrome (ZES) (205 without and 30 with prior acid-reducing surgery) and compared the results with 984 patients from 182 reports in the literature. The aims of the study were to evaluate the sensitivity of proposed acid secretory criteria for the diagnosis of ZES, propose new criteria, evaluate the variability and methodology of gastric secretory testing, and correlate the symptoms and signs of ZES, tumor extent, and primary tumor size and location with the degree of gastric acid hypersecretion. Multiple endocrine neoplasia-type 1 (MEN1) occurred in 22% of patients. The mean basal acid output (BAO) in patients without and with prior acid-reducing surgery was 41.2 +/- 1.7 mEq/hr (range, 1.6-118.3 mEq/hr) and 27.6 +/- 3.5 mEq/hr (range 5.9-102.9 mEq/hr), respectively. In patients with MEN1, those with female gender, Hispanic, or Asian race had lower BAOs. Diarrhea, esophageal stricture, and pyloric scarring were associated with a higher BAO. Neither other symptoms nor the tumor extent, primary tumor location, or size correlated with the magnitude of acid hypersecretion. ZES diagnosis was delayed a mean of 5.5 +/- 0.4 yr. Patients who were misdiagnosed as having either Crohn or celiac disease had higher BAOs. The sensitivities from our study and the literature review of the proposed BAO criteria for the diagnosis of ZES in patients without previous gastric acid-reducing surgery were 91% and 90% for BAO > or = 15 mEq/hr, 86% and 82% for BAO > or = 18 mEq/hr, 69% and 67% for BAO > 25 mEq/hr, and < 60% for BAO > 31 mEq/hr, respectively. The specificities of all the proposed BAO criteria were high. Both the criterion of BAO > or = 15 mEq/hr and BAO > or = 18 mEq/hr had good specificities and equal sensitivity. With prior acid-reducing surgery, the sensitivities in our study and from the literature review were 100% and 81% for BAO > or = 5 mEq/hr, 73% and 45% for BAO > 14.4 mEq/hr, and 37% and 31% for BAO > 19.2 mEq/hr, respectively. The reported mean specificity for the criterion of BAO > or = 5 mEq/hr was 85%, while it was 100% for the other 2 criteria. The maximal acid output (MAO) criterion of > 70 mEq/hr had sensitivities in the present National Institutes of Health (NIH) study and the literature review of 39% and 31%, respectively, and the criterion of MAO > 100 mEq/hr had a sensitivity of < 15% in patients with no prior acid-reducing surgery. The proposed criterion of BAO/MAO ratio > 0.6 had a low sensitivity. The proposed criterion of the ratio of basal and maximal acid H+ concentration (BAC/MAC ratio) > or = 0.6 had an excellent sensitivity-- > or = 89% in patients with or without previous acid-reducing surgery. The reported specificity for both the BAO/MAO criterion and the BAC/MAC criterion were similar, but BAC/MAC had a better sensitivity. Combination criteria of BAO generally did not improve sensitivity. The criterion of pH < or = 1 was met by only 27% of patients, and pH < or = 0.96 by 21% of patients with previous acid-reducing surgery. For patients with MEN1 with no prior acid-reducing surgery, the sensitivities were lower compared with patients with the sporadic form of ZES. The mean gastric volume in patients without prior acid-reducing surgery was 314 +/- 10 mL/hr and 247 +/- 25 mL/hr in patients with prior acid-reducing surgery. A basal volume criteria of > 160 mL/hr in patients without prior acid-reducing surgery occurred in > 86% of patients, and > 140 mL/hr in 87% of patients with prior acid-reducing surgery; these, thus, are neglected findings that have good sensitivities. Our analysis shows criteria based on MAO, pH, and BAO/MAO ratio do not have high sensitivities and thus are not useful. In patients without prior acid-reducing surgery, the criteria of BAO > or = 15 mEq/hr, BAC/MAC ratio > or = 0.6, and basal gastric volume > 160 mL/hr are useful for the diagnosis of ZES and have good specificities. In patients with prior acid-reducing surgery, the criteria of BAO > or = 5 mEq/hr, BAC/MAC ratio > or = 0.6, and basal gastric volume > 140 mL/hr have high sensitivities. In patients with sporadic ZES without acid-reducing surgery, the criterion of BAO > or = 18 mEq/hr is recommended as it has a similar sensitivity but higher specificity than the criterion of BAO > or = 15 mEq/hr. Only 1 patient in either data set (NIH or the literature) with or without previous acid-reducing surgery had a basal gastric pH > 2, therefore this finding essentially excludes the diagnosis of ZES. Gastric secretory measurements for 30 minutes, but not 15 minutes, give results comparable to those for a full hour. On the basis of these results, a number of gastric secretory criteria are proposed, including some for the first time, and alterations in methodology are proposed that should prove useful in the diagnosis of ZES.     

Use of omeprazole in patients with Zollinger-Ellison syndrome

Omeprazole, a substituted benzimidazole, has been shown to be a potent inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome (ZES). We review our experience, as well as the published data on 210 patients with ZES who have required omeprazole for control of gastric acid hypersecretion over the past seven years. The dose of omeprazole required in individual patients ranged from 10 to 180 mg/24 hr with 20-60% requiring a split dosage regimen. Omeprazole was effective in approximately 99% of the patients over a period ranging from 0.5 to 54 months. Twenty-four percent of patients required an increase in omeprazole dose, while 26% required a decrease in dose. Adverse effects attributable to omeprazole were reported in 2% of patients, and in all cases, they were mild (ie, rash, constipation, headache). There was no effect of omeprazole on serum gastrin concentration or on gastric endocrine cells in three studies. Although one patient with multiple endocrine neoplasia, type-I syndrome (MEN-I) in this series developed a gastric carcinoid while taking omeprazole, evidence is presented that suggests the presence of MEN-I per se may be important in determining the development of gastric carcinoid in patients with ZES. It is concluded that omeprazole is safe and effective in patients with ZES, and in these patients, it is the drug of choice for the management of gastric acid hypersecretion. However, yearly assessment is indicated to clearly evaluate the long-term risk of gastric carcinoid as well as therapy directed at the gastrinoma itself.     

Efficacy of pantoprazole 20 mg daily compared with esomeprazole 20 mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial - the EMANCIPATE study

OBJECTIVES: To compare the efficacy and tolerability of pantoprazole 20 mg once daily with that of esomeprazole 20 mg once daily for 6 months as maintenance therapy in patients with previously healed gastroesophageal reflux disease. METHODS: In an initial open-label acute phase, outpatients with endoscopically confirmed gastroesophageal reflux disease (Los Angeles grades A-D) received pantoprazole 40 mg once daily for 4 or 8 weeks. Those healed (defined as the absence of esophagitis, and 'no' or 'mild' heartburn and acid regurgitation) were randomized in the double-blind manner for maintenance therapy with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily for 6 months. RESULTS: In the acute healing phase, 1452 patients were recruited to receive pantoprazole 40 mg once daily. Healing success was 91% (intent-to-treat analysis). A total of 1303 patients entered the maintenance phase of the study. Pantoprazole 20 mg once daily and esomeprazole 20 mg once daily were equally effective at maintaining patients in remission; 84 and 85% of pantoprazole and esomeprazole recipients remained in combined endoscopic and symptomatic remission at 6 months (intent-to-treat analysis). The confidence interval of the difference was (-5.7; +infinity), showing that pantoprazole is as effective as esomeprazole with a noninferiority margin of 5.8%. Combined endoscopic and symptomatic remission was independent of Helicobacter pylori status. Both treatments were well tolerated and safe. CONCLUSION: Treatment with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily provides similarly effective and well-tolerated maintenance of previously healed gastroesophageal reflux disease irrespective of baseline H. pylori status.     

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study

OBJECTIVES: Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. METHODS: This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. RESULTS: Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.     

The efficacy of the third pump inhibitor--pantoprazole--in the short-term treatment of Chinese patients with duodenal ulcer.

BACKGROUND/AIMS: To study the efficacy and tolerability of pantoprazole 40 mg once daily before breakfast compared with ranitidine 300 mg once daily at bedtime in Chinese patients with duodenal ulcer, and to evaluate the relationship between Helicobacter pylori (H. pylori) clearance and ulcer healing rate. METHODOLOGY: A total of 160 patients (80 in each group) with endoscopically diagnosed, active duodenal ulcers were studied in this randomized double-blind trial. Endoscopy was performed after 2 weeks of treatment. If unhealed, then the patients were re-endoscoped after an additional 2 weeks of similar treatment. RESULTS: The healing rates after 2 and 4 weeks were 61.3% and 97.3%, respectively in the pantoprazole group, and 50.7% and 76.9% in the ranitidine group. The difference between the two groups was significant at 4 weeks (p < 0.01, per protocol analysis). The rate of pain free ulcer was higher in the pantoprazole group than in the ranitidine group at 2 weeks (84.2% vs. 59.6%, p < 0.01). Higher clearance of H. pylori was also observed in the pantoprazole group compared with the ranitidine group at 4 weeks (20% vs. 0%, p = 0.05). The healing rate tended to be higher in patients who were H. pylori-cleared at 2 weeks (p = 0.07) in the pantoprazole group. Both medications were well tolerated without any serious adverse effects. CONCLUSIONS: Pantoprazole 40 mg daily is superior to ranitidine 300 mg daily in the short-term treatment of acute duodenal ulcer in Chinese patients, in terms of ulcer healing and pain relief, and appears to be well-tolerated.     

Assessment of effectiveness of different dosage regimens of pantoprazole in controlling symptoms and healing esophageal lesions of patients with mild erosive esophagitis

BACKGROUND: Gastroesophageal reflux disease is a very common affection, and esophageal involvement is particularly frequent. The means to effectively control symptoms and improve esophageal inflammation in these patients is to reduce esophageal acid exposure. For this purpose, we use gastric proton pump inhibitor, that can suppress gastric acid secretion. AIM: To compare the effectiveness of two different pantoprazole dosage regimens (20 and 40 mg/day), in controlling symptoms and healing esophageal lesions of patients with mild erosive esophagitis. MATERIAL AND METHODS: Fifty-seven patients with endoscopically confirmed mild erosive esophagitis characterized as non-confluent erosions in the distal esophagus, were randomly to be treated either with pantoprazole 20 mg/day (group I, 28 patients) or 40 mg/day (group II, 29 patients) over a period of 4 weeks. After treatment completion, the patients were assessed for clinical and endoscopic outcome, i.e., absence of erosions in distal esophagus and improvement of gastroesophageal reflux symptoms. RESULTS: At the end of the treatment, 73.1% of the patients in group I and 85.7% of the patients in group II had endoscopic improvement. We also observed, that 88.5% of the patients in group I and 92.9% of the patients in group II had complete elimination of heartburn and regurgitation. CONCLUSION: Pantoprazole dosage regimens of 20 mg/day and 40 mg/day provide equivalent effectiveness in controlling symptoms and healing esophageal lesions of mild esophagitis.     

Efficacy and safety of pantoprazole in patients with gastroesophageal reflux disease using an intravenous-oral regimen. Austrian Intravenous Pantoprazole Study Group.

BACKGROUND/AIMS: To investigate the efficacy and safety of an intravenous-oral regimen using the gastric proton pump inhibitor pantoprazole. METHODOLOGY: Outpatients, with endoscopically diagnosed moderate or severe gastro-esophageal reflux disease (GERD stage II and III, respectively, Savary-Miller classification), were recruited from ten hospitals or private practice centers and enrolled into an open-labeled study (intention-to-treat population n=110, age 20-88 years; per-protocol population n=98). Patients were treated once daily with 40 mg pantoprazole which was administered as an intravenous injection for the initial 5-7 consecutive days, then as a tablet, for up to 8 weeks. The efficacy parameters were complete healing of lesions evaluated endoscopically after week 4 and 8, and relief from symptoms assessed after week 2 and 4. RESULTS: Complete healing was achieved in 85/98 (87%) and 93/98 (95%) per-protocol patients, after 4 and 8 weeks, respectively. The corresponding results for the intention-to-treat population were 85/110 (77%) and 93/110 (85%), respectively. After 2 weeks of treatment, heartburn, acid regurgitation, and pain on swallowing resolved in 97%, 98%, and 100% of the per-protocol patients, respectively. Faster healing was observed in non-smokers, those infected with Helicobacter pylori, and those with initial GERD stage II. The intravenous and oral administration phases were well tolerated. CONCLUSIONS: Pantoprazole (40 mg), applied as an intravenous-oral regimen to patients with GERD led to fast resolution of symptoms and high healing rates. For patients, temporarily unable to take oral medications, this regimen offers safe and reliable gastric acid suppression and allows the possibility of changing between the oral and intravenous administration without the need for dose adjustment.