Vijaya Pratha

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-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.

Human Proximal Duodenal Alkaline Secretion Is Mediated by Cl-/HCO3- Exchange and HCO3- Conductance

The proximal duodenal epithelium secretesbicarbonate into an adherent mucus layer, therebyprotecting the mucosa from injury by gastric acid andpepsin. While bicarbonate secretion is stimulated andinhibited by a number of agonists and antagonists, theapical anion transport pathways have not been addressedfully. The objective was to assess if apicalCl-/HCO3- exchange andCl-:HCO3- conductanceare involved in duodenal mucosal bicarbonate secretion(DMBS). In healthy volunteers, the proximal 4 cm ofduodenum was isolated, perfused with either saline or4,4′-diisothiocyano-2,2′-disulfonic acid(DIDS), and bicarbonate secretion and transepithelial potentialdifference (PD) were stimulated by eitherPGE2 or the phosphodiesterase inhibitortheophylline to increase cyclic AMP. Luminal DIDSabolished PGE2-stimulated DMBS, yet had no effect on the increase in PD andfailed to significantly alter theophylline-induced DMBSand PD. Therefore, in human proximal duodenum, itappears that PGE2 and cAMP activate distinctHCO transport pathways 2 likely involving a DIDS-sensitiveCl-/HCO3- exchanger andDIDS-insensitive HCO3-conductance.

Utility of endoscopic biopsy samples to quantitate human duodenal ion transport.

Duodenal mucosal bicarbonate secretion (DMBS) prevents acid-peptic damage and facilitates nutrient absorption. DMBS is diminished in patients with duodenal ulcers and is normalized after Helicobacter pylori eradication. The measurement of DMBS in human patients in vivo requires intubation with a multi-lumen balloon tube and permits limited testing with putative agonists and antagonists. Our purpose was to develop a means to investigate transport events in human duodenal biopsy samples in vitro. After validation studies in a modified mini-Ussing chamber were performed, duodenal transport events were examined in proximal endoscopic biopsy samples from normal volunteers (n = 17). Tissues were mounted in modified mini-Ussing chambers (volume 2.5 ml, surface area 3.8 mm2). Short circuit current (Isc), potential difference (PD), and bicarbonate secretion were determined under basal conditions and after stimulation with graded doses of prostaglandin E2 (PGE2)(10(-8) to 10(-4) mol/L) and dibutyryl cAMP (db-cAMP)(10(-4) to 10(-2) mol/L). Duodenal tissues remained viable for at least 2 hours and exhibited stable basal HCO3(-) secretion and electrical parameters. Stimulation with PGE2 and db-cAMP resulted in dose-related increases in both Isc and HCO3(-) secretion (P < .05) that were abolished by ouabain and anoxia. It is concluded (1) that human duodenal bulb biopsy samples maintain their inherent transport function in mini-Ussing chambers and (2) that by using this novel method it will be possible to define the transport events that modulate human duodenal secretion, in particular bicarbonate secretion, in both health and disease.

Gastric pH above 2.5 is of limited use as a measure of acid inhibition

Purpose: Acid in the gastric refluxate is a key contributor to mucosal injury in GERD. Hence, quantification of gastric acid secretion is a logical measure of efficacy of medical therapy for GERD. Gastric acid output (GAO = [H+] gastric volume) measures actual gastric acid secretion. However, intragastric pH is frequently used to assess the efficacy of proton pump inhibitor therapy. The purpose of this study was to assess the accuracy of intragastric pH as a measure of gastric acid secretion and potential esophageal acid load.

Pantoprazole effectively decreases the number of long reflux episodes by day 1 of therapy

Purpose: Erosive GERD patients with more severe disease frequently have prolonged esophageal mucosal contact of the refluxate. The lack of clearance results in increased exposure to acid that causes mucosal damage. Therefore, decreasing the number of reflux episodes lasting longer than 5 minutes should be an important factor in healing severe disease and treating associated symptoms. This analysis was performed to assess the effect of pantoprazole on the number of long reflux episodes in patients with severe erosive GERD.

Pantoprazole positively impacts nighttime heartburn symptoms and quality of sleep in patients with gastroesophageal reflux disease

Pantoprazole positively impacts nighttime heartburn symptoms and quality of sleep in patients with gastroesophageal reflux disease

Pantoprazole is more effective than ranitidine in reducing the duration of esophageal acid contact

Pantoprazole is more effective than ranitidine in reducing the duration of esophageal acid contact