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.     

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.     

Inhibition of pentagastrin-induced gastric acid secretion by intravenous pantoprazole: a dose-response study

OBJECTIVE: The purpose of this study was to compare the gastric acid inhibitory ability of increasing doses of intravenous (i.i.) pantoprazole with that of i.v. famotidine and placebo. Pentagastrin was infused continuously in healthy subjects as a model for patients with Zollinger-Ellison syndrome. METHODS: Pentagastrin (1 microg/kg/h) was infused to stimulate maximum acid output in 39 subjects over a 25-h period. After 60 min of pentagastrin infusion, subjects received a single dose of i.v. pantoprazole (20, 40, 80, or 120 mg), i.v. famotidine (20 mg), or saline placebo. The variables measured were onset of response (time until acid output fell to < 10 mEq/h), duration of response (time acid output remained < 10 mEq/h), and cumulative acid output over 24 h. RESULTS: All doses of i.v. pantoprazole produced a dose-dependent suppression of acid output to < 10 mEq/h. Single i.v. doses of pantoprazole, 80 and 120 mg, suppressed acid output by > 90% in all subjects for < or = 21 h and had an onset of action of < 1 h. CONCLUSIONS: Intravenous pantoprazole has a rapid onset and a clear dose-related effect, with a significantly longer duration of action than that of i.v. famotidine.     

Intravenous omeprazole in patients with Zollinger-Ellison syndrome undergoing surgery

Twenty patients with Zollinger-Ellison syndrome who were undergoing surgery were studied prospectively to assess the efficacy and safety of IV omeprazole. During the preoperative period, in 19 of 20 patients, omeprazole 60 mg administered as an IV bolus every 12 hours inhibited acid output to less than 5 mEq/h measured in the last hour before the next dose of drug. In one patient, acid output was 25 mEq/h 12 hours after omeprazole, 60 mg, and increasing the dose to 100 mg every 12 hours reduced acid output to less than 5 mEq/h. During the operative and postoperative periods, IV omeprazole controlled gastric acid hypersecretion in all patients for up to 15 days. During this time, all patients received the dose determined preoperatively. No patient developed any clinical, hematological, or biochemical toxicity that could be attributed to omeprazole therapy during the preoperative or postoperative period. The present study demonstrates that omeprazole administered by IV bolus is safe and effective for controlling gastric acid hypersecretion. In contrast to IV histamine H2-receptor antagonists, IV omeprazole has the advantages of not requiring continuous infusion or postoperative dose adjustments. Intravenous omeprazole will become the drug of choice in patients with Zollinger-Ellison syndrome undergoing surgery.     

Idiopathic gastric acid hypersecretion presenting as a diarrheal disorder and mimicking both Zollinger-Ellison syndrome and Crohn's disease

Many gastric acid hypersecretory states (basal acid output of greater than 15.0 mEq/h) exist for which the etiology is known, such as Zollinger-Ellison syndrome, systemic mastocytosis, antral exclusion, antral predominant Helicobacter pylori gastritis (antral G cell hyperplasia), chronic gastric outlet obstruction, short gut syndrome and basophilic leukemias. However, many hypersecretory patients have no identified etiology for their acid hypersecretion and are designated as idiopathic gastric acid hypersecretors with a basal acid output of greater than 10 mEq/h and a normal serum gastrin level. Because of the gastric acid hypersecretion these patients also commonly have an increased frequency of stools. Idiopathic gastric acid hypersecretion represents a known cause of gastric acid hypersecretion that is far more common than Zollinger-Ellison syndrome and it has a markedly different treatment regimen and natural history. We report a case of a patient with idiopathic gastric acid hypersecretion previously misdiagnosed as having Crohn's disease because of a presenting complaint of diarrhea and mimicking Zollinger-Ellison syndrome because her fasting serum gastrin level was elevated when incorrectly measured in the presence of antisecretory treatment.     

Oral pantoprazole for acid suppression in the treatment of patients with Zollinger-Ellison syndrome.

BACKGROUND: The management of patients with gastric acid hypersecretion due to gastrinoma, usually recognized as Zollinger-Ellison syndrome (ZES), was radically changed 10 years ago by the use of proton pump inhibitors. Surgical treatment now concentrates on tumour excision, and in the majority of patients, gastrectomy is no longer required to prevent complications of acid hypersecretion that can be managed pharmacologically. AIMS: To verify the ability of pantoprazole to control gastric acid hypersecretion and the clinical effects of acid hypersecretion in seven patients with documented ZES. METHODS: Pantoprazole was administered at an initial dose of 80 mg daily for seven days before basal acid output (BAO) was measured at 08:00, ie, 1 h before the next dose of pantoprazole was normally ingested. A lower (40 mg) or higher (120 mg or more) dose of pantoprazole was then used to keep the BAO in the therapeutic range (between 0.1 and 10 mmol/h) and to control clinical symptoms such as acid-related pain or diarrhea. RESULTS: BAO and clinical symptoms were controlled with pantoprazole 40 mg daily in one patient, 80 mg daily in two patients, 120 mg daily in three patients and 160 mg daily in one patient. CONCLUSIONS: Pantoprazole was able to control acid hypersecretion in ZES patients when administered in doses between 40 and 160 mg daily. An initial dose of 120 mg given before further titration of the drug regimen appears to be a reasonable therapeutic strategy.     

Parenteral antisecretory drug therapy in patients with Zollinger-Ellison syndrome

Forty-six patients with Zollinger-Ellison syndrome were studied prospectively to determine a safe and effective method and criterion for controlling gastric acid hypersecretion during periods when oral antisecretory agents could not be used. In each patient it was possible to reduce acid secretion to less than or equal to 10 mEq/h after an i.v. bolus of 150 or 300 mg of cimetidine and a stepwise titration of cimetidine given by continuous infusion. The mean dose given by i.v. infusion was 2.9 mg/kg body wt.h but there was a wide range (0.5-7.0 mg/kg body wt.h) and the minimal dose had to be determined individually for each patient. The minimal i.v. cimetidine dose did not correlate with basal or maximal acid output or fasting gastrin concentration, but correlated closely with either the previous oral dose of cimetidine (r = 0.96, p less than 0.001) or the previous oral dose of ranitidine or famotidine (r = 0.95, p less than 0.001). To study the efficacy and safety of an i.v. infusion of cimetidine, 34 patients undergoing surgery were maintained on i.v. cimetidine for a mean of 12 days (range 1-83 days). One-half of the patients did not require dose adjustment, whereas the remainder required an average of 2 adjustments, usually in the first 3 postoperative days. No patient developed complications attributable to gastric acid hypersecretion in the postoperative period, and there was no detectable neurologic, hematologic, or hepatic toxicity. This study demonstrates that a continuous i.v. infusion of cimetidine adequately inhibits gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. However, high doses were frequently required, the dose had to be determined in a stepwise fashion individually for each patient, and the i.v. dose correlated with the previous oral dose. Reducing acid secretion to less than or equal to 10 mEq/h was a safe criterion during surgery and continuous i.v. cimetidine was safe and effective in achieving this degree of control for up to 83 days.     

Oral and intravenous dosage forms of pantoprazole are equivalent in their ability to suppress gastric acid secretion in patients with gastroesophageal reflux disease

OBJECTIVE: The aim of this study was to assess the ability of pantoprazole to maintain gastric acid suppression in patients with gastroesophageal reflux disease who are switched from an oral (p.o.) to an intravenous (i.v.) dosage form. METHODS: A total of 65 patients with gastroesophageal reflux disease were administered either 40 or 20 mg of p.o. pantoprazole daily for 10 days, then were switched to either a matching dose of i.v. pantoprazole or to placebo for 7 days. Acid output (basal and maximal) was measured at the end of the p.o. treatment period and on the first and last days of i.v. therapy. In the primary efficacy analysis, the acid output values at the end of the p.o. pantoprazole treatment were compared with those at the end of the i.v. treatment. Safety was monitored by periodic vital sign measurements, clinical laboratory evaluations, ophthalmic examinations, electrocardiograms, and reports of adverse events. The data were tested by an analysis of covariance and by Wilcoxon signed rank and t tests. RESULTS: Maximal acid output (mean +/- SD) in the 40 mg and 20 mg pantoprazole group after p.o. treatment was 6.5 +/- 5.6 mEq/h and 14.5 +/- 15.5 mEq/h, respectively; whereas, at the end of the i.v. treatment period, the values were 6.6 +/- 6.3 mEq/h and 11.1 +/- 10.2 mEq/h, respectively. In patients given i.v. placebo, acid output was significantly (p < 0.05) increased to 29.2 +/- 13.0 mEq/h by day 7. Both p.o. and i.v. pantoprazole dosage forms had similar favorable safety and tolerability profiles. CONCLUSIONS: The p.o. and i.v. formulations of pantoprazole (40 and 20 mg) are equivalent in their ability to suppress gastric acid output. The i.v. form of pantoprazole offers an alternative for gastroesophageal reflux disease patients who are unable to take the p.o. formulation.     

Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: a prospective study

We examined prospectively the criteria for medical management in 16 patients with Zollinger-Ellison syndrome who had had previous gastric surgery. Each patient received sufficient antisecretory medication to lower gastric acid output to less than 10 mEq/h during the last hour before the next dose of drug. The 7 patients with a vagotomy but no gastric resection were symptom-free and had no mucosal disease. Of 9 patients with a partial gastrectomy, 7 had mucosal disease, with or without symptoms, and 6 of the 7 patients had acid outputs of 5-10 mEq/h. In these patients, antisecretory medication was increased to reduce output to less than 5 mEq/h and symptoms and mucosal abnormalities resolved in each patient. Patients with Zollinger-Ellison syndrome and a vagotomy can be treated safely by reducing acid secretion to less than 10 mEq/h, but in patients with a partial gastrectomy, acid secretion must be reduced to less than 5 mEq/h, and adequacy of therapy must be checked further by endoscopy.     

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.     

Idiopathic gastric acid hypersecretion

Many patients with acid-peptic disease have idiopathic gastric acid hypersecretion defined as a basal acid output >10.0 meq/hr; however, a significant proportion have basal acid outputs >15.0 meq/hr, which is within the range found in Zollinger-Ellison syndrome. Although idiopathic gastric acid hypersecretion is more common than Zollinger-Ellison syndrome, it is important that these two disorders be differentiated because of differences in treatment and natural history. In the present study, we compared 124 patients with idiopathic gastric acid hypersecretion and 137 patients with Zollinger-Ellison syndrome. There were no significant differences with regard to age at diagnosis, history of upper gastrointestinal hemorrhage, nausea, vomiting, and family history of duodenal ulcer and other acid-peptic disease. However, significant differences were observed between patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome with regard to percentage of males: 77% compared to 64% (P=0.008), mean serum gastrin: 60 pg/ml compared to 3679 pg/ml (normal <100 pg/ml) (P<0.001), mean basal acid output: 15.4 meq/hr compared to 47.0 meq/hr (P<0.001), mean age at onset of symptoms: 33 years compared to 41 years (P<0.001), mean duration of symptoms before diagnosis: 11 years compared to five years (P<0.001), percentage with abdominal pain: 67% compared to 82% (P=0.00004), percentage with diarrhea: 12% compared to 75% (P<0.000001), percentage with pyrosis: 58% compared to 40% (P=0.003), percentage with duodenal ulcer: 53% compared to 74% (P<0.000001), and percentage with esophagitis: 31% compared to 42% (P=0.0004). The differences in clinical features could be attributed to difference in mean basal acid output, and/or differences in levels of basal acid output used for diagnosis of idiopathic gastric acid hypersecretion (basal acid output >10.0 meq/hr) and Zollinger-Ellison syndrome (basal acid output >15.0 meq/hr). When 45 patients with idiopathic gastric acid hypersecretion and 39 patients with Zollinger-Ellison syndrome with basal acid outputs 15.1–30.0 meq/hr were compared, the main significant differences were with regard to mean serum gastrin: 69 pg/ml compared to 655 pg/ml (P<0.001), percentage of male gender: 82% compared to 62% (P=0.03), and percentage with diarrhea: 16% compared to 64% (P=0.000005). These results indicate that in general patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome often have similar clinical features that can be difficult to distinguish. However, the increased frequency of diarrhea and female gender should lead to a strong suspicion of Zollinger-Ellison syndrome, which can be distinguished in almost every case by measurement of serum gastrin.     

Omeprazole: effective, convenient therapy for Zollinger-Ellison syndrome

The acute and long-term effects of omeprazole on gastric acid secretion were examined in 11 patients with Zollinger-Ellison syndrome. Basal gastric acid secretion was inhibited by 50% 3 h after a single 60-mg dose of omeprazole and 78% 4 h after administration of omeprazole. Patients were treated with a single daily dose of omeprazole, and the dose requirement was defined as the lowest dose of omeprazole that would reduce gastric acid secretion to less than 10 mEq/h during the last hour before the next dose. The mean daily dose requirement was 70 mg (range 20-160 mg). Ten of the 11 patients were given omeprazole once a day and 1 patient required omeprazole every 12 h. When omeprazole was discontinued after several months of therapy, mean basal gastric acid secretion was inhibited by greater than 50% 48 h after administration of omeprazole. Omeprazole continued to inhibit gastric acid secretion during 1-9 mo of therapy and patients remained free of toxicity or side effects related to omeprazole. Omeprazole is a highly effective inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome. Because of its potency and long duration of action, omeprazole offers an advance in convenient medical therapy for Zollinger-Ellison syndrome compared with the histamine H2-receptor antagonists.     

Reflux esophagitis in patients with Zollinger-Ellison syndrome

The incidence of ulcers of the stomach and duodenum and their response to medical therapy, in patients with Zollinger-Ellison syndrome is well described. However, reflux esophagitis is less well recognized. In this study we determined the frequency of reflux esophagitis in 122 patients with Zollinger-Ellison syndrome and examined their response to medical therapy. Esophageal symptoms, endoscopic abnormalities, or both were present in 61% of patients. Forty-five percent of patients had esophageal symptoms consisting of heartburn, dysphagia, or both. Forty-three percent of patients had endoscopic abnormalities of the esophagus, and 23% demonstrated moderate or severe disease. When sufficient antisecretory medication was administered to lower gastric acid secretion to less than 10 mEq/h in the last hour before the next dose of drug, 67% of the patients with reflux esophagitis responded with complete disappearance of symptoms and normalization of the endoscopic abnormalities. The other 33% of patients required an increase in medication to lower acid output to less than 5 mEq/h in 7% and less than 1 mEq/h in the other 26% to resolve symptoms and signs completely. We conclude that reflux esophagitis occurs in the majority of patients with Zollinger-Ellison syndrome and responds well to medical therapy, although one third of patients require intensive antisecretory medication.     

Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study

To determine the long-term efficacy, safety, and toxicity of omeprazole, we studied 40 patients with Zollinger-Ellison syndrome given omeprazole for 6-51 mo (median 29). The mean daily dose of omeprazole required to control gastric acid secretion was 82 +/- 31 mg. Thirty-one patients required omeprazole once per day. In 9 patients acid output was not controlled by 120 mg once per day, but was controlled by 60 mg every 12 h. The daily dose of omeprazole correlated with the previous dose of histamine H2-receptor antagonist (r = 0.89, p less than 0.001), basal acid output (r = 0.43, p less than 0.01), and maximal acid output (r = 0.39, p less than 0.02) but not with serum concentration of gastrin (r = -0.32). Increases in the dose of omeprazole were required in 9 patients. Twenty-nine patients had mild peptic symptoms with acid outputs less than 10 mEq/h while taking histamine H2-receptor antagonists. Symptoms resolved completely in 23 patients and partially in 3 when taking omeprazole. Omeprazole prevented mucosal disease in all patients including 17 in whom histamine H2-receptor antagonists had produced only partial resolution despite acid output being less than 10 mEq/h and in those with symptoms during omeprazole therapy. Omeprazole therapy was not associated with any significant side effects, nor with any evidence of hematologic or biochemical toxicity. Serum concentrations of gastrin did not change significantly during therapy. In 6 patients treated with omeprazole for 1 yr there was no change in basal or maximal acid output. In all patients, gastric morphology and histopathology demonstrated no evidence of gastric carcinoid formation. These results demonstrate that with long-term treatment of up to 4 yr, omeprazole is safe, with no evidence of hematologic, biochemical, or gastric toxicity. Furthermore, omeprazole remained effective, with only 23% of patients requiring an increase in dose, and continued to control symptoms in patients who had not been entirely symptom-free despite high doses of histamine H2-receptor antagonists. Omeprazole is now the drug of choice in patients with Zollinger-Ellison syndrome.     

Effect of pantoprazole versus other proton pump inhibitors on 24-hour intragastric pH and basal acid output in Zollinger-Ellison syndrome

AIM: In this open prospective study, the efficacy of pantoprazole in reducing gastric acid secretion in Zollinger-Ellison syndrome patients was compared to that obtained previously with other proton pump inhibitors.METHODS: Eleven male patients previously treated with omeprazole (n=7, mean dosage: 63 mg/day; range: 20-100 mg/day) or lansoprazole (n=4, mean dosage: 75 mg/day; range: 30-120 mg/day) were included. These patients underwent a 24-hour intragastric pH-metry, measurement of basal acid output and of serum gastrin first while receiving their usual therapy and second after 7 to 10 days of pantoprazole treatment at a mean dosage of 116 mg/day (range: 40-200 mg/day). Basal acid output was evaluated after each intragastric pH-metry, one hour before the next intake of proton pump inhibitor and a serum gastrin curve was determined according to 9 fixed time points.RESULTS: One patient dropped out before the second intragastric pH-metry due to an adverse event (varicella) unrelated to pantoprazole and was reinvestigated thereafter. The median 24-h intragastric pH with pantoprazole was not significantly different than that with the other proton pump inhibitors (5.3 versus 4.6, respectively; P=0.90). Neither the median basal acid output values nor the median serum gastrin levels were significantly different between pantoprazole and the other proton pump inhibitors.CONCLUSION: In these patients with the Zollinger-Ellison syndrome, pantoprazole was well tolerated and equally effective to the other proton pump inhibitors in terms of antisecretory potency.     

Definition for idiopathic gastric acid hypersecretion

Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic gastric acid hypersecretion were developed. Sixty-five normal subjects were evaluated to define idiopathic gastric acid hypersecretion on a statistical basis, and 22 patients with refractory duodenal ulcers were evaluated to define idiopathic gastric acid hypersecretion on a functional basis. Mean basal acid output for the 65 normal subjects was 3.0±2.7 meq/hr. Even though the mean basal acid output for the group of 28 normal male subjects was slightly higher than for the group of 37 normal female subjects, the groups were not significantly different. The 95% confidence interval around the mean basal acid output for all normal subjects was 2.4–3.7 meq/hr, with little difference between the male and female groups. The mean basal acid output plus two standard deviations and the mean basal acid output plus three standard deviations for the 65 normal subjects were 8.4 meq/hr and 11.1 meq/hr, respectively. Of 109 patients with active duodenal ulcers treated for eight weeks with standard doses of antisecretory medication, 22 showed no healing as documented by endoscopy. The mean basal acid output for these 22 patients with nonhealed duodenal ulcers was 18.7 meq/hr (range 10.1–49.1 meq/hr) while mean basal acid output for the 87 patients with healed duodenal ulcers was 7.5 meq/hr (range 0.0–27.9 meq/hr). The difference in mean basal acid output between these two groups was statistically different (P<0.001). All patients with refractory duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Our results indicate that the definition for idiopathic gastric acid hypersecretion should be a basal acid output of greater than 10.0 meq/hr, since, based on refractory duodenal ulcer disease, the functional definition for idiopathic gastric acid hypersecretion is a basal acid output of greater than 10.0 meq/hr, which in our data also corresponds well to the statistically defined range of basal acid output in normal subjects.     

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.     

Ranitidine therapy in patients with idiopathic gastric acid hypersecretion

One hundred twenty-four patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) were prospectively evaluated and treated with ranitidine twice a day. Fifty-four patients (44%) required standard doses of ranitidine 300 mg/day for adequate treatment, and the other 70 patients (56%) required increased doses of ranitidine (mean 994 mg/day, range 600–3000 mg/day). Mean basal acid outputs for these two groups were 14.0 and 16.6 meq/hr, respectively, which were not significantly different. Nevertheless, there was a significant correlation between basal acid output and daily ranitidine dose required for therapy (r=0.18,P=0.05). The duration of ranitidine therapy consisted of: <1 year (N=46), 1 year (N=16), 2 years (N=19), 3 years (N=22), 4 years (N=15), 5 years (N=6). Only five patients required progressive increases in ranitidine during the time of treatment, which consisted of an average of 0.5 dose adjustments per year. No side effects occurred with any of these high doses of ranitidine. These results indicate that, as in Zollinger-Ellison syndrome, ranitidine is effective therapy for patients with idiopathic gastric acid hypersecretion; however, markedly increased doses as large as 3000 mg/day may be required.     

Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome

In the present study we explored whether the presence or absence of symptoms could provide a reliable way of assessing the adequacy of control of gastric secretion in patients with Zollinger-Ellison syndrome who were treated medically. Over a 5-yr period, 26 Zollinger-Ellison syndrome patients were entered into a prospective study which examined the presence or absence of symptoms that are associated with gastric hypersecretion, the presence of absence of upper gastrointestinal pathology, and the degree of control of gastric acid secretion. During their last admission, 15 of the 26 patients (58%) were symptomatic, but post-drug gastric acid secretion for the 2 h before the next dose of medication was not significantly different from that in asymptomatic patients. This lack of correlation between the presence or absence of symptoms and post-drug gastric acid secretion was evident for the group as a whole, as well as for 8 to 12 patients who underwent multiple admissions. Of 23 patients who underwent upper gastrointestinal endoscopy of x-ray, or both, on their last admission, 12 had pathology. Post-drug gastric acid secretion was less in patients without pathology than in those with pathology. Furthermore, in patients in whom post-drug gastric acid secretion was less than or equal to 10 mEq/h, the criterion of acceptable control used in this study, pathology did not occur. These findings demonstrate that the presence or absence of symptoms cannot be used to assess the adequacy of medical control of gastric acid secretion in patients with Zollinger-Ellison syndrome. In our opinion, maintenance of post-drug gastric acid secretion less than or equal to 10 mEq/h for the 2 h before the next dose of medication is an acceptable criterion for long-term control of gastric secretion in patients with Zollinger-Ellison syndrome.     

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.