Nocturnal Acid Breakthrough Research Articles

DEVELOPMENT AND OPTIMIZATION OF RABEPRAZOLE CHRONO-MODULATED DRUG DELIVERY SYSTEMS

Objective: Development and optimization of chrono-modulated pulsatile drug delivery systems (CPDDS) loaded with Rabeprazole for treating nocturnal acid breakthrough in ulcer patients was set as the major objective of this work. Methods: CPDDS were developed to provide drug release as two pulses with predetermined gap. Separate microparticles for delayed instant release (DIR) and delayed extended-release (DER) were formulated. Through the optimization of several formulation and process parameters, ER microparticles were created as matrix microspheres. Central composite design was used to understand how the factors affected the responses. The optimized ER microspheres and plain drug were separately subjected to enteric coating to obtain DER and DIR portion microparticles, respectively. Results: With the exception of stirring speed's impact on drug release, every other factor was found to have a significant influence (p<0.05) on every response. The mechanism underlying the Rabeprazole's delayed prolonged release was explained by the SEM images. The microspheres made with Eudragit RSPO at 0.72 g and polyethylene oxide at 0.5 g for 1 g of Rabeprazole at 400 rpm were shown to be the optimal formulation based on the graphical optimization results. After being coated with a terminal enteric coating, this formulation showed delayed release for a duration of 6 h. Conclusion: After oral administration of equal doses of DIR microcapsules along with the optimized DER microspheres could release Rabeprazole effectively as two different pulses at the desired time intervals.

Efficacy and Safety of Omeprazole for the Treatment of Acid Peptic Disorders: A Systematic Review and Meta-Analysis

Background Aim. To compare the efficacy of omeprazole to other proton-pump inhibitors (PPIs) or placebo for the treatment of acid peptic disorders (APDs) using a comprehensive literature search including hard-to-access journals and non-English articles. Methods. PubMed, Google Scholar, and China National Knowledge Infrastructure were searched (from inception to March 2023) for trials comparing omeprazole to other types of PPIs or placebo for the treatment APD. Efficacy was analyzed separately for erosive diseases and nonerosive diseases. Primary outcomes included improvement of APD symptoms and frequency of ulcer or erosion healing. Secondary outcomes included adverse events, cost effectiveness, nocturnal acid breakthrough, and length of stay if hospitalized. Random and fixed-effects models were used to determine estimates of efficacy. Results. Thirty-one eligible trials (N = 10,539 participants) were analyzed, including 12 articles not typically included in previous reviews due to translation or journal access issues. Omeprazole significantly improved heartburn compared to placebo (RR = 2.47, 95% CI: 2.13 and 2.86, and p<0.001) and was equivalent to the other five types of PPI. Omeprazole had significantly fewer patients reporting adverse events versus placebo (11% versus 31%, respectively) and other PPIs. Omeprazole was the most cost-effective PPI compared to the other types of PPIs in India. Conclusions. Omeprazole continues to be an effective proton-pump inhibitor to treat patients with acid peptic disorders and was well tolerated. Omeprazole was significantly better than placebo and was equivalent with other PPIs for curing heartburn and was equivalent to other PPIs for the healing of ulcers or erosions in addition to being the most cost-effective.

Acid-suppressive drugs: A systematic review and network meta-analysis of their nocturnal acid-inhibitory effect.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs). To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA). Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB. This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

Pharmacokinetic and pharmacodynamic exploration of various combinations of tegoprazan immediate and delayed-release formulations.

The new modified-release formulation of tegoprazan, a novel potassium-competitive acid blocker, is expected to improve the management of acid-related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinations of tegoprazan with immediate-release (IR) and delayed-release (DR) formulations. A three-cohort, open-label, randomized, single-dose, three-treatment, six-sequence, three-period crossover study was conducted. Various combinations of tegoprazan IR and DR formulations (50, 75 or 100 mg) were administered orally once per period. The 24-h intragastric pH was monitored before and after each administration. PK blood samples were collected for up to 48 h. PK and PD were compared among treatments. Eighteen healthy Korean subjects completed the study. All treatment groups showed intragastric pH above 4 approximately 1h following tegoprazan administration. Among the various combinations, the IR and DR combination at a 1:1 ratio induced greater gastric acid suppression (%Time pH ≥ 4) than IR alone in each dose group, both for 24 h (50 mg; 59% vs. 52%, P = .2188, 95% confidence interval [CI] -6.92-22.27, 100 mg; 85% vs. 70%, P < .05, 95% CI 8.92-22.19) and at night (50 mg; 27% vs. 16%, P = .1563, 95% CI -11.79-37.71, 100 mg; 77% vs. 49%, P < .05, 95% CI 16.14-42.98), with similar systemic exposure. The combinatorial tegoprazan in the IR and DR 1:1 ratio formulation was found to induce stronger gastric acid suppression throughout the day and at night, compared to the conventional IR formulation.

Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects.

Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation. The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.

Novel Esomeprazole Magnesium-Loaded Dual-Release Mini-Tablet Polycap: Formulation, Optimization, Characterization, and In Vivo Evaluation in Beagle Dogs.

Esomeprazole magnesium (EMP) is a proton pump inhibitor (PPI) that reduces acid secretion. EMP has a short plasma half-life (approximately 1.3 h); hence, nocturnal acid breakthrough (NAB) frequently occurs, disturbing the patient’s nighttime comfort and sleep. We aimed to develop a novel esomeprazole magnesium-loaded dual-release mini-tablet polycap (DR polycap) with a prolonged onset time and improved bioavailability to prevent NAB. The formulation of the EPM mini-tablet core resulted in rapid drug release. The core was coated with an inner coating and an Eudragit® L30D-55 aqueous dispersion coating to prepare the first-release mini-tablet. In addition, the core was coated with an inner coating and an aqueous dispersion of Eudragit® S100 and Eudragit® L100 coating to prepare the second-release mini-tablet. Each mini-tablet type was characterized using an in vitro dissolution test and microscopic examination. After testing, 10 of each mini-tablets were placed together in hard capsules to form DR polycaps. The combination of mini-tablets was optimized via in vitro release testing and in vivo pharmacokinetic studies. The AUC0–24h of the DR polycap was similar to that of a comparable commercial product (Nexium®); Cmax was lower by approximately 50%, and Tmax was extended by approximately 1.7-fold. In conclusion, DR polycap is an alternative to commercial products with improved NAB and dosing compliance because of its dual-release characteristics.

Nocturnal acid breakthrough and esophageal acidification during treatment with dexlansoprazole as compared to omeprazole in patients with gastroesophageal reflux disease.

Nocturnal acid breakthrough (NAB) may differ based on duration of proton pump inhibitor (PPI) action and Helicobacter pylori (H. pylori) infection; NAB may influence esophageal acidification (EA) and mucosal damage. Dexlansoprazole, a long-acting PPI, was not compared with omeprazole for NAB, gastric acid suppression, and EA in relation to H. pylori infection. In this prospective open-label comparative observational study, gastroesophageal reflux disease (GERD) patients were evaluated using 24-h dual-channel pH-impedance monitoring while on dexlansoprazole (60 mg, n = 39) and omeprazole (20 mg, n = 41) to study the degree of gastric acid suppression, esophageal acid exposure, and NAB (primary outcome measures). H. pylori was detected by rapid urease test and histology. NAB tended to be frequent with omeprazole than dexlansoprazole (33/41 [80.5%] vs. 23/39 [59%]; p = 0.06). Though nocturnal mean esophageal pH was comparable between the dexlansoprazole and omeprazole groups, its duration was less with the former (181.5 [15.2-334.2] vs. 283 [158-366] min, p = 0.03). NAB was as frequent in the H. pylori-infected than the non-infected group (11/19 [57.9%] vs. 45/61 [73.8%]; p = 0.1). The nocturnal gastric and esophageal pH in the H. pylori-infected group was higher than in the non-infected group (4.6 ± 1.7 vs. 4 ± 1.6, p = 0.157; 6.1 ± 0.6 vs. 5.8 ± 0.6, p = 0.128). Dexlansoprazole tended to increase 24-h and nocturnal mean gastric pH among H. pylori-infected more than omeprazole (5.9 ± 1.1 vs. 4.2 ± 1.7, p = 0.023; 5.7 ± 1.2 vs. 3.8 ± 1.5, p = 0.006). Dexlansoprazole is more effective than omeprazole in suppressing gastric acid secretion, resulting in lesser EA and NAB, particularly in the presence of H. pylori.

Night-time gastric acid suppression by tegoprazan compared to vonoprazan or esomeprazole.

AimsNocturnal acid breakthrough has been considered an unmet need of proton‐pump inhibitors. Tegoprazan, a novel potassium‐competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night‐time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid‐suppressive effects.MethodsA randomized, open‐label, 3‐period, 6‐sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.ResultsSixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night‐time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night‐time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.ConclusionTegoprazan produced more rapid, potent and well sustained night‐time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.

24-HOUR ESOPHAGEAL MULTICHANNEL PH-IMPEDANCE MONITORING IN THE DIAGNOSIS OF GASTROESOPHAGEAL REFLUX DISEASE (CLINICAL CASES)

Background. Gastroesophageal reflux disease (GERD) is an urgent problem of modern gastroenterology as well as the most common pathology of the upper gastrointestinal tract; it is a chronic disease that significantly reduces the patient's quality of life, increases the risk of developing Barrett's esophagus and esophageal adenocarcinoma. Objective. To assess the potentials of multichannel intraluminal pH impedance monitoring in the diagnosis of esophageal diseases. Material and methods. In 3 patients with clinical and endoscopic signs of GERD esophageal multichannel intraluminal pH-impedance monitoring was performed using the diagnostic equipment Digitrapper pH-Z from Given Imaging (USA). Results. 24-hour esophageal pH monitoring enabled to verify the diagnosis of GERD, to reveal a hypersensitive esophagus and manifestations of nocturnal acid breakthrough. Conclusions. Multichannel intraluminal pH-impedance monitoring is the "gold standard" for the diagnosis of esophageal diseases; it significantly expands opportunities of gastroenterologists in the treatment of GERD.

Tegoprazan to treat gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the United States. Although proton pump inhibitors (PPIs) are the mainstay of therapy for GERD and its complications, they have several limitations, including incomplete symptom resolution. Potassium-competitive acid blockers (P-CABs) were developed to address the limitations of PPIs as well as the need for improved antisecretory effects. Tegoprazan, the newest P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and nonerosive reflux disease (NERD). A highly selective inhibitor of the H+/K+-ATPase, tegoprazan is also safe and effective for nocturnal acid breakthrough (NAB) and motility. Further studies of tegoprazan are warranted to define its potential role in the treatment of acid-related disorders.

Gastrointestinal Involvement in Systemic Sclerosis: An Update.

Gastrointestinal Involvement in Systemic Sclerosis: An Update.

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

Background/AimsThough nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole.MethodsFifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded.ResultsOf the 58 patients (age 35.5 [inter-quartile range 26.5–46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9–4.1] vs 5.7 [4.6–6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0–1.0] vs 0.0 [0.0–0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1–2, n = 19] vs 1 [range 1–3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0–315] vs 159 [69–287] minutes, P = 0.500; 1.02 [0.7–1.4] vs 1.04 [0.44–1.3], P = 0.620, respectively).ConclusionsThough NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

Augmentation of Permeability of Drugs having P-Glycoprotein Inhibition for Efficiency in Nocturnal Acid Breakthrough

Purpose : Ranitidine is a BCS class III drug having low oral, lipophilicity and is susceptible to the Pglycoprotein (P-gp) efflux mechanism. Permeation enhancers enhance the bioavailability of ranitidine by increasing the partition coefficient (K oct/buffer there by increasing the lipophilicity and permeability. The main) aim of the present work is to overcome the problems of ranitidine bioavailability by expending permeation enhancers and P-gp inhibitors. Methodology : The existence of synergistic activity in permeation enhancement effect was studied using EDTA, citric acid, oleic acid, caprylic acid, sodium glycocholate and sodium deoxycholate. The P-gp inhibitor used here was felodipine, a first generation inhibitor showed P-gp inhibition activity at a concentration where it shows it pharmacological action. Three formulations were formulated and subjected to various physiochemical evaluations like weight variation, friability, hardness, drug content, in vitro drug release and kinetic studies.A continuous dissolution-absorption system was designed using everted intestine segment. Results : Synergistic effect in enhancing the permeability of ranitidine was found to exist between chelating agents in combination with fatty acids and its derivatives. From the precompression parameters data of the lubricated blend, it was found that the flow ability was good and can be compressed into tablets by direct compression method. The formulated ranitidine immediate release tablets exhibited first order release kinetics, resulting in rapid and complete release for two h. Conclusion : The effective drug permeability (P eff ) after three h or formulations TAB, TAB37, TAB37-PGP and TAB-MARK is 2.60, 3.17, 3.66 and 2.68, respectively. This shows that the permeability through chick intestine is more from TAB37-PGP by increased P-gp inhibition.

Possibilities of pH impedance and high-resolution manometry in managing patients with refractory gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common condition that has a substantial impact on quality of life in patients and is a leading risk factor for esophageal adenocarcinoma. Now therapy with proton pump inhibitors (PPIs) is a basic method in the treatment of patients with GERD; however, one third of the patients do not respond to the therapy used. The causes of refractory GERD are a fairly large group of heterogeneous factors contributing to the inefficacy of PPIs in adequate dosage. Among these factors, there is low compliance by patients to the prescribed treatment regimen; nocturnal acid breakthrough; СУР2С19 gene polymorphism; chiasm syndrome with functional diseases of the gastrointestinal tract; non-acidic refluxes in a patient; thoracic esophageal motility disorders; the increased number and duration of transient lower esophageal sphincter relaxation periods; hiatus hernia; and misdiagnosis. 24-hour pH impedance and high-resolution esophageal manometry are now the most informative diagnostic techniques in patients who fail to respond to PPI therapy. These techniques allow one to timely recognize the causes of refractory GERD, to make a differential diagnosis with other nosological entities, and to timely correct therapy for each individual patient.

Laryngopharyngeal reflux disease (LPRD) –Review article-

Laryngopharyngeal reflux disease (LPRD) is caused by the back-flow of stomach contents and/or gastric acid into the laryngopharynx. Symptoms of laryngopharyngeal reflux (LPR) include hoarseness, sore throat, throat-clearing, chronic cough, globus sensation, dysphagia, and postnasal drip. LPRD is diagnosed in approximately 10% of patients presenting to outpatient otolaryngology clinics and in more than 50% of patients presenting with voice complaints. Gastroesophageal reflux disease (GERD) and LPRD may be associated with periodontitis, sleep disorders, and otolaryngology disease.Gastric acid reflux with LPRD is thought to cause laryngeal granulomas.The most useful endolaryngeal signs for diagnosing LPRD are erythema, edema, and interarytenoid hypertrophy. Ambulatory 24-h dual-probe pH monitoring can be misleading; false-positive outcomes may occur due to artifacts in the upper probe, and false-negative outcomes can occur as a result of the intermittent character of reflux episodes. In patients with LPRD, proton pump inhibitors (PPIs) have been shown to significantly improve reflux laryngitis. However, some patients are resistant to antacid therapy. Nocturnal acid breakthrough (NAB) on PPI has been suggested as one reason for resistance to PPI therapy. Administration of a PPI with the additional bedtime administration of a histamine-2 receptor antagonist has been shown to be an effective treatment of LPRD with NAB. Recently, potassium-competitive acid blockers have been proposed as an effective treatment of antacid-resistant disease.

The Effect of H2 Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy.

The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H+, K+-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.

Editorial: towards extended acid suppression - the search continues

Editorial: towards extended acid suppression - the search continues

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

BackgroundObesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects.MethodsGastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances.Results24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001).ConclusionsIn asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole.Trial registrationClinicalTrial.gov: NCT01136317

Primary Care Practitioners’ Views on the Use of Proton Pump Inhibitors Associated with Alginate-Antacids for Better Gastroesophageal Reflux Disease Symptom Control: Results of a National Survey in Spain

Background: Gastroesophageal reflux disease (GERD) is a prevalent disease in Western countries. Despite effective treatment modalities, in some patients total symptom control is not achieved in clinical practice. A cross-sectional study was designed to assess primary care practitioners’ views on the effectiveness of proton pump inhibitors (PPI) as monotherapy in the control of the most common symptoms of GERD (heartburn and regurgitation), as well as to determine the level of implementation of the “combined therapy” (PPI + alginate-antacids). Methods: A questionnaire on different aspects of the management of GERD was completed by 1491 primary care physicians. The questionnaire was composed of 11 close-ended questions with one-choice answer, with a total of 52 items, covering the main data from patients presenting with GERD. Results: Treatment with PPI alone was mostly considered insufficient for the control of GERD symptoms. The combined treatment of PPI + alginate-antacids was used for 37% and 21% of physicians for treating heart-burn and regurgitation, respectively. A better control of symptoms, an increase in the onset of action and to reduce nocturnal acid breakthrough were the most frequently argued reasons for the use of PPI + alginate-antacids. A high percentage of participants believed that treatment with PPI alone was insufficient for the control of symptoms and 39.8% of physicians reported the persistence of heartburn, 38.6% the persistence of regurgitation and 43.2% the persistence of epigastric discomfort in more than 25% of their patients treated with PPI as monotherapy. The most common schedule for the use of the antacid medication was on demand. Conclusions: Spanish primary care physicians consider that a high proportion of GERD patients continue to suffer from symptoms during PPI treatment alone. Ondemand “combined therapy” (PPI + antacid) is considered an efficient option to control reflux symptoms still troublesome in patients with PPI treatment alone.

Innovative techniques in evaluating the esophagus; imaging of esophageal morphology and function; and drugs for esophageal disease

This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB).