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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Morphometric estimation of acid output in duodenal ulcer associated with Helicobacter pylori infection.

OBJECTIVE: to determine the changes in acid output before and after eradication therapy in patients with duodenal ulcer associated with Helicobacter pylori infection. METHOD: the subjects of this prospective study were 16 patients with acute duodenal ulcer at endoscopy and H. pylori infection determined by rapid urease test and histology. They were randomly assigned to receive treatment with pantoprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. during 7 or 14 days. Endoscopic examination and biopsy were repeated 4 weeks after treatment ended. The changes in acid output before and after treatment were calculated by the morphometric quantification of parietal cell canaliculi from the gastric corpus. To this end 20 parietal cells from the medial glandular zone were selected and canalicular index was calculated, before and after eradication therapy, with a morphometric method based on automatic analysis of histological images. RESULTS: canalicular index was 26.4 +/- 1.4 (mean +/- standard error of the mean) before treatment, and 20.5 +/- 1 (p < 0.01) after therapy. CONCLUSIONS: morphometric analysis showed a decrease in acid output in patients with duodenal ulcer associated with H. pylori infection 4 weeks after eradication therapy with clarithromycin, amoxicillin and pantoprazole.     

Intravenous Pantoprazole as Initial Treatment in Patients With Gastroesophageal Reflux Disease and a History of Erosive Esophagitis: A Randomized Clinical Trial

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.     

Sensitivity, specificity and predictive values of the secretin infusion test in the diagnosis of gastrinoma

From 1974 to 1981, 55 patients, 18 with Zollinger-Ellison syndrome (ZES) histologically confirmed and 37 patients with duodenal ulcer (DU) without pylorostenosis were followed for a minimal period of 5 years. The diagnostic values of a) basal acid output (BAO mEq/h); b) 60 min acid output after secretin infusion, 3 CU-GIH/kg, (MAO-SE mEq/h); c) basal serum gastrin (BSG pg/ml: mean of 4 gastrin determinations) and d) serum gastrin after secretin (SG-SE pg/ml: mean of 4 gastrin determinations during secretin infusion) were calculated. Cut off point values of 100 p. 100 specificity (i. e. no DU patient reached these values) with a positive predictive value of 100 p. 100 (i. e. probability for gastrinoma when this cut off point was attained) were BAO greater than 26 mEq/h, MAO-SE greater than 18 mEq/h, BSG greater than 221 pg/ml, SG-SE greater than 186 pg/ml. The sensitivities of these parameters (i. e. percent of ZES which reached the given cut off point) were respectively (p. 100): 39, 78, 72 and 94. Ranking these parameters according to their own discriminative value expressed by R2 (square correlation coefficient) gave SG-SE, R2 = 0.559; BSG, R2 = 0.508; MAO-SE, R2 = 0.456; BAO, R2 = 0.414. The most discriminative association of 2 variables was SG-SE and MAO-SE (R2 = 0.650). Association of SG-SE, MAO-SE and BAO or BSG (or BAO and BSG) did not increase significantly the discrimination between ZES and DU (R2 = 0.672).     

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.     

Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential

OBJECTIVE: Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. METHODS: The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during 1-h parafilm- and 1-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. RESULTS: The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 +/- 0.59 vs 2.75 +/- 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 +/- 0.73 vs 2.22 +/- 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 +/- 6.4 vs 109 +/- 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 +/- 6.1 vs 132 +/- 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 +/- 73 vs 271 +/- 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 +/- 92 vs 675 +/- 168 ng/h). CONCLUSIONS: Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may play a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion.     

Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion

AIMS: To determine the influence of recommended therapeutic doses of pantoprazole and omeprazole on meal-stimulated acid secretion. METHODS: In this double-blind, placebo-controlled, three-period crossover study, 12 healthy male volunteers received 40 mg pantoprazole od, 20 mg omeprazole od or placebo at 08:00 h for 5 days in a randomized order. Meal-stimulated acid secretion was determined by means of a homogenized test meal, and intragastric titration on day 1, 4-6 h, 8-10 h, 16-18 h, and 24-26 h, and on days 3 and 5, 4-6 h after oral drug administration. RESULTS: On day 1 (4-6 h after oral drug administration), meal-stimulated acid secretion was decreased by 36% and 24% after administration of 40 mg pantoprazole or 20 mg omeprazole, respectively. After 3 and 5 days of dosing, the decreases were 88% and 85% with 40 mg pantoprazole, and 70% and 74% with 20 mg omeprazole. At all measuring points during the 5-day dosing periods, 40 mg pantoprazole proved superior to 20 mg omeprazole in inhibiting meal-stimulated gastric acid secretion. The differences were statistically significant for pantoprazole on day 1, 24-26 h after oral drug administration and on day 3 (P = 0.0425 and P = 0.0244, respectively). On day 1, only pantoprazole was significantly better than placebo (P = 0.0210, 4-6 h after dosing; P = 0.0093, 8-10 h after dosing and P = 0.0068, 16-18 h after dosing). CONCLUSION: Pantoprazole 40 mg is significantly more effective than omeprazole 20 mg in inhibiting meal-stimulated acid secretion. In addition, pantoprazole exhibits a more rapid onset of action.     

Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS)

STUDY OBJECTIVE: To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0.1-N hydrochloric acid. SETTING: Hospital in-patients in university medical center. PATIENTS: Ten consecutive male patients with AIDS. INTERVENTION: Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1-N hydrochloric acid. MEASUREMENTS AND MAIN RESULTS: Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration-time curve was below normal (1.4 +/- 0.9 mg/h.L; mean +/- SE), and absorption was normalized by hydrochloric acid (9.9 +/- mg/h.L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 +/- 6.7 mg/h.L). CONCLUSIONS: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients.     

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.     

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure

BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN 相似文献   

Lack of effect of gastric acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir in HIV-infected patients

Recent studies have shown that coadministration of certain protease inhibitors (PIs) with gastric acid-reducing agents results in decreased plasma concentrations of the PI. To assess the effect of acid-reducing agents on lopinavir/ritonavir, data from two clinical trials (n = 38 and 190) were pooled. Both trials randomized antiretroviral-na?ve, HIV-infected patients to receive lopinavir/ritonavir 400/100 mg twice-daily or 800/200 mg once-daily in combination with stavudine and lamivudine, or tenofovir and emtricitabine. Concurrent administration of gastric acid-reducing agents including antacids of various brand names, proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole), and H(2)-receptor antagonists (ranitidine, famotidine, cimetidine, and nizatidine) was reported in both trials. Lopinavir and ritonavir pharmacokinetic parameters were evaluated. Thirty subjects were considered users of acid-reducing agents at the times of pharmacokinetic evaluation. HIV-infected patients who received gastric acid-reducing agents during administration of lopinavir/ritonavir-based treatment regimens did not appear to have a reduction in lopinavir or ritonavir exposures.     

Intragastric pH during continuous infusion with pantoprazole in patients with bleeding peptic ulcer

OBJECTIVES: In managing patients with bleeding peptic ulcers, prevention of rebleeding is a particular challenge to hemostasis and fibrinolysis, both of which involve reactions that are impaired in acidic gastric environment. Therefore, such patients are expected to benefit from profound acid suppression. The present investigation aimed to establish a safe and, with regard to pH elevation, effective treatment that, based on in vitro evidence, should provide clinical benefit in this patient population. METHODS: Patients with acute bleeding peptic ulcers (Forrest Ia, Ib, IIa) after successful endoscopic hemostasis were enrolled in two pilot studies (N = 20 each). They were given an intravenous bolus injection of 80 mg of pantoprazole immediately followed by continuous infusion of either 6 mg/h or 8 mg/h pantoprazole for 72 h. Intragastric pH was measured continuously over 24 h and, if possible, for up to 48 h. RESULTS: Intragastric pH increased rapidly to values of about 6 with both treatments. For the 0-24 h period, the median pH values were 6.1 (68% range 4.5-7.4) and 6.1 (68% range 5.2-6.7) in patients receiving 6 mg/h and 8 mg/h continuous infusion, respectively; the values for the 0-48 h period were 5.9 (4.9-6.7) and 6.3 (5.5-7.0), respectively. The median percentage time that pH was > or =6 during the 0-48 h interval was 47% (68% range 28-89) for the 6 mg/h treatment group and 64% (68% range 41-84) for the 8 mg/h treatment group. Both treatment regimens with pantoprazole were well tolerated based on electrocardiographic measurements, vital signs, clinical laboratory values, and adverse events. CONCLUSIONS: Compared with the infusion with 6 mg/h pantoprazole, the continuous infusion of 8 mg/h pantoprazole showed a lower interindividual variability of the intragastric pH and a greater percentage of time that pH was >/ or =6. Thus, with regard to safety and efficacy, an initial 80-mg bolus injection, followed by 8 mg/h continuous infusion, seems to be the adequate treatment in patients with a high risk of rebleeding.