Intragastric Acidity Research Articles

The Role of the Acid Pocket in Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease is one of the commonest chronic conditions in the western world and its prevalence is increasing worldwide. The discovery of the acid pocket explained the paradox of acid reflux occurring more frequently in the postprandial period despite intragastric acidity being low due to the buffering effect of the meal. The acid pocket was first described in 2001 when it was detected as an area of low pH immediately distal to the cardia using dual pH electrode pull-through studies 15 minutes after a meal. It was hypothesized that there was a local pocket of acid close to the gastroesophageal junction that escapes the buffering effect of the meal, and that this is the source of postprandial acidic reflux. The presence of the acid pocket has been confirmed in other studies using different techniques including high-resolution pHmetry, Bravo capsule, magnetic resonance imaging, and scintigraphy. This review aims to describe what we know about the acid pocket including its length, volume, fluid constituents, and its relationship to the lower esophageal sphincter and squamocolumnar junction. We will discuss the possible mechanisms that lead to the formation of the acid pocket and examine what differences exist in patients who suffer from acid reflux. Treatments for reflux disease that affect the acid pocket will also be discussed.

Increased Post-Prandial Intragastric and Duodenal Acidity in Patients With Chronic Pancreatitis Could Result in Duodenitis

A 29 year old Hispanic male with history of DM type 1, Type V hyperlipoproteinemia, and chronic pancreatitis with exocrine insufficiency came to the ER complaining of abdominal pain. His abdominal pain had started 2 days ago, 6/10, periumbilical, radiated to the back, dull in nature, not related to food, intermittent at first, but was constant for the last 1 day. On review of systems, he complained of subjective fever, chills, diaphoresis, nausea, 2-3 episodes of non-bloody, non-bilious vomiting, loss of appetite, about 20 lbs wt loss over 3 months, and dark-colored stools. Pertinent findings on physical examination were no pallor or icterus, diffuse abdominal tenderness on palpation without rebound or guarding with good bowel sounds and no organomegaly, and digital rectal examination showed good anal sphincter with no gross blood. His significant laboratory findings were hemoglobin and hematocrit of 8.7/25.4 with lipase of 28. He was admitted to general medical floor for acute on chronic pancreatitis. He was aggressively treated with intravenous normal saline. In view of his anemia, esophagogastroduodenoscopy (EGD) was performed. EGD showed erythema antrum of the stomach and duodenitis and biopsy showed mild chronic inflammation in the gastric mucosa but no helicobacter pylori and no villous blunting in the duodenum. Subsequently, he was started on protonix 40mg po daily and iron supplements. Furthermore, his symptoms improved and he tolerated oral diet and was discharged home to follow-up in GI clinic. In the postprandial periods intraduodenal pH has been shown to be markedly reduced in chronic pancreatitis patients. Intragastric pH is also lower in chronic pancreatitis patients. When focusing on the percentage of postprandial time with pH below five in the duodenum and pH below three in the stomach, chronic pancreatitis patients were exposed to acid in stomach and duodenum for a significantly longer period. Several previous studies have measured intraduodenal pH in patients with chronic pancreatitis and all have observed an abnormally low intraduodenal pH with reduced acid neutralizing capacity.

Editorial: towards extended acid suppression - the search continues

Editorial: towards extended acid suppression - the search continues

Endoscopic Suturing for Ulcer Exclusion in Patients With Massively Bleeding Large Gastric Ulcer

Bleeding peptic ulcer is one of the most important causes for hospitalization worldwide. Though endoscopic hemostasis is the current standard of treatment for bleeding peptic ulcers, ulcer rebleeding remained a chief cause of mortality.1Chiu P.W. et al.Clin Gastroenterol Hepatol. 2009; 3: 311-316Abstract Full Text Full Text PDF Scopus (88) Google Scholar One of the important strategies to improve outcomes for bleeding peptic ulcers is to prevent rebleeding. Indeed, endoscopic features for ulcers with high risk of rebleeding include ulcers larger than 2 cm, actively bleeding and those located at posterior duodenal bulb or high lesser curvature.2Johnston J.H. et al.Gastroenterology. 1987; 92: 1101-1108Abstract Full Text PDF PubMed Scopus (111) Google Scholar With the use of high-dose intravenous proton pump inhibitors (PPI), those who developed rebleeding after PPI infusion were patients with significant perioperative risks, high proportion of comorbidities, as well as older age which rendered them high-risk surgical candidates.3Elmunzer B.J. et al.Am J Gastroenterol. 2008; 103: 2625-2632Crossref PubMed Scopus (119) Google Scholar A prototype endoscopic suturing device had been investigated for the safety and efficacy in achieving hemostasis among massively bleeding gastric ulcers.4Chiu P.W. et al.Dig Surg. 2009; 26: 243-248Crossref PubMed Scopus (16) Google Scholar This is an initial report on the clinical application of surgical ulcer exclusion using endoscopic suturing for large bleeding gastric ulcer. The Apollo Overstitch is an endoscopic suturing system which consists of a cap-based suturing system with a curved suture arm extending from one of the dual channels and the anchor exchange system extending from the same channel. The handle to control the suture plication system was mounted onto the shaft of a double-channel endoscope (Olympus 2T100 scope, Olympus Co Ltd, Hong Kong). The Overstitch system attached to the double-channel endoscope was introduced into the stomach through an overtube. The bleeding ulcer was first located with an ordinary single-channel endoscope. Endoscopic suturing begins with the needle first driving through the distal edge of the bleeding ulcer. After closing the curved needle driver, the detachable needle should be grasped by the anchor exchange and detached from the needle driver. After opening the needle driver, the endoscope with Overstitch should be moved away from the distal ulcer edge. The needle should be placed back in the needle driver by the anchor exchange. The needle should then be driven over the proximal edge of the ulcer and the procedure repeated until the 2 edges of the ulcer can be pulled together. The needle anchor should be dropped, while the anchor exchange is replaced by the cinching device which passes along the 2 ‘O’ polypropylene suture. After passage of the cinch to ulcer edge, the polypropylene suture should be tightened against the end of the cinch. The cinch is then closed to cut the stitch and release the plug to tighten the suture, and the ulcer should be excluded from an intragastric high acidity environment to stop current bleeding and prevent rebleeding. Three patients received endoscopic ulcer exclusion for a massively bleeding gastric ulcer. This video shows endoscopic suturing for ulcer exclusion in an actively bleeding gastric ulcer. The patient was a 78-year-old man who presented with passage of tarry stool for 3 days; upper endoscopy showing a 2 cm large gastric ulcer at angular incisura with visible vessel. There was active bleeding from visible vessel (Figure 1). The Overstitch device was introduced through an overtube. The first suture plication was performed over the superior edge of the ulcer. After exchange of the anchor, the second suture plication was performed over the inferior ulcer edge. This process was continued until a figure of eight suture was formed over the ulcer. The anchor was then dropped and the suture was tightened with the cinching device. The ulcer was excluded with adequate hemostasis (Figure 2). The patient had no clinical evidence of rebleeding, and a repeated endoscopy in 72 hours confirmed secure closure of the ulcer.Figure 2Ulcer exclusion achieved after tightening of overstitch.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Surgical exclusion of bleeding ulcer is a conventional treatment for prevention of further bleeding through suture closure of the ulcer and excluding it from intragastric acidity. This is the first technological report on clinical application of endoscopic surgical suturing for ulcer exclusion. The success of endoscopic ulcer exclusion will lead to improvement in primary endoscopic hemostasis, and theoretically excluding the ulcer from acid to prevent further bleeding. The ulcer exclusion shall be a better method to prevent rebleeding compared with adjunctive high-dose proton pump inhibitor infusion or prophylactic angiographic embolization. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0NDRlMDkxM2NmMGRhNGUwNGJiZDFkODUyMjRjMjQxYyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjgxMzYwNDY3fQ.XXJzrp-6yqa5X_Fxu-t93ZJmJ4gGt5KEIICkg-xZWs2P9QUVTwPcWU5BIAoyY161WQqS9Xoq2xlMpMeFIa03TVHD9haMAQ-SBed6va3cMQtozXytNgaNMojGDSQwMA4hN2-dG7kGlLfGkDlU3dV9Oi0epZaZBfhQIxkNVWPYU76Fm68LSNLJ7_1G29qT5DlWZrSOHsW10o5dkts0yBD9W0Bc9PUUOiJX1P41J4-g2lAv77tNCIPyZNrVzhbQnAt1xIYBD1YAb1HHnXEHF1q2P_ISMMsqrfBJmW0OLGH8PblHrNNDwqnDn3pnyRIekdVxovny7vwoogxhrPzxLQT2mw Download .mp4 (43.03 MB) Help with .mp4 files Video 1

Calcium Carbonate Breath Test for Non-Invasive Estimation of Gastric Acid Secretion

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO₃) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO₂), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO₃ breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO₃ breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO₂ concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO₃ breath test values well reflected the fasting intragastric acidity. The ¹³CO₂ concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO₃ breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO₃ breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO₃ breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

Randomized, Placebo-Controlled, Crossover Pharmacodynamic Study Comparing the Effects of Zegerid® Capsule to Prevacid® Delayed-Release Capsule

Purpose: The primary objective was to evaluate the difference in the onset of action between two PPIs in fasting subjects on the seventh day of treatment. The secondary objectives included evaluations such as the difference in the onset of action in fasting subjects on the 1st day of treatment, the median time to an intragastric pH >4.0 for 10 consecutive minutes after drug administration on day 1 and day 7 of treatment, etc. Methods: Subjects were healthy male or female non-Asian adults within the age range of 18-65 years. Subjects were randomized to a three-way crossover to either Zegerid Capsules (20 mg omeprazole/1100 mg sodium bicarbonate), Prevacid Capsules (15 mg lansoprazole), or no-treatment. The treatment or no-treatment periods were 7 days. There was a minimum two-week washout period between treatments. Subjects underwent a 24-hour intragastric pH study on the first and seventh days of each period. A total of 63 subjects were randomized, and 59 completed per protocol. The primary efficacy endpoint was the earliest time for which a statistically significant difference between the median intragastric pH scores for three consecutive five-minute intervals at steady-state on day 7. Secondary efficacy endpoints included evaluation of primary efficacy endpoint on day one, determination of the time to sustained difference in inhibition of intragastric acidity between the two active study treatments on day 1 and day 7, etc. A total of 14 subjects experienced 21 treatment-emergent adverse events. Results: Zegerid achieved significant difference over Prevacid on day 7 for all of the five-minutes postdose intervals beginning at the 10-15 minute interval (p = 0.0242) and sustaining through the 115-120 minute interval (p = 0.0170). On day 7, over the 24-hour period, Zegerid maintained pH > 3.5 and 4 significantly longer than Prevacid (p=0.0075), and held the pH > 3.5 and 4 more than 50% of the time (at least 12 hours; p=0.0209). Zegerid maintained the pH >4 significantly longer than Prevacid during the first four hours after dosing, with the first dose on day 1 (p= 0.0021), and the last dose on day 7 (p <0.0001). Conclusion: Zegerid capsules provide a significantly stronger acid suppressing pharmacodynamic effect, both in onset and duration of effect, than Prevacid capsules. The results also confirmed significant pH control over placebo in both active treatments. Both Zegerid and Prevacid were safe and well-tolerated. Disclosure - Dr. McGraw, and O'Mullane are employees of Merck. Dr. Pratha is a Merck consultant, and was the investigator. Mr. Tobin is employed by the CRO that provided study support services for Merck (performed the analyses, etc.). This research was supported by an industry grant from Merck.

Intragastric acidity and omeprazole exposure during dosing with either PA32540 (enteric‐coated aspirin 325 mg + immediate‐release omeprazole 40 mg) or enteric‐coated aspirin 325 mg + enteric‐coated omeprazole 40 mg – a randomised, phase 1, crossover study

Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325mg and immediate-release (IR) omeprazole 40mg. Immediate-release omeprazole (located in outer layer of tablet) is available for instantaneous dissolution rapidly after ingestion, while dissolution of the EC-ASA core is delayed until pH >5.5. To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325mg + IR-omeprazole 40mg) vs. enteric-coated (EC)-omeprazole 40mg. This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7days of once-daily dosing with PA32540 with 7days of once-daily EC-ASA 325mg + EC-omeprazole 40mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid. Twenty-six subjects (mean age 29years) were enrolled into the study. On Day 7, mean per cent time intragastric pH >4 was 50.6% for PA32540 and 57.6% for EC-omeprazole 40mg (P=0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446h*ng/mL for PA32540 and 2558h*ng/mL for EC-omeprazole 40mg. Day 7 median Tmax of omeprazole was 0.5h for PA32540 and 1.25h for EC-omeprazole 40mg. Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20mg.

817 DCLK1 Labels Adult Pancreatic Progenitor and Cancer Initiating Cells

G A A b st ra ct s secretion volume despite significant decrease in intragastric acidity. Gastric secretion accumulates on the top of the liquid meal forming a "floating" layer. We assume that this layer is the correlate for the so called "acid pocket", which has previously been assumed according to several pH pull-through studies− the term "pocket" therefore being an unfavourable description. This phenomenon may be an important factor in the pathogenesis of GERD and in the persistence of GERD symptoms under PPI.

815 An Insertion of Eight Amino Acids in HLA-DQA1 and Three Amino Acid Substitutions in HLA-DQA1 and HLA-DQB1 Confer Risk to Idiopathic Achalasia

G A A b st ra ct s secretion volume despite significant decrease in intragastric acidity. Gastric secretion accumulates on the top of the liquid meal forming a floating layer. We assume that this layer is the correlate for the so called acid pocket, which has previously been assumed according to several pH pull-through studies− the term pocket therefore being an unfavourable description. This phenomenon may be an important factor in the pathogenesis of GERD and in the persistence of GERD symptoms under PPI.

The Innovative Potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to Restore the “Gastric Barrier Effect” in Patients Chronically Treated With PPI

Gastroesophageal reflux disease is a very widespread condition. In Europe, it is estimated that about 175 million people suffer from this disease and have to chronically take drugs to increase gastric pH. The proton pump inhibitors (PPIs) such as omeprazole, lansoprazole, and esomeprazole are the most widely used drug typology in this regard. However, the inhibition of normal gastric acid secretion has important side effects, the most important being bacterial overgrowth in the stomach and duodenum with a concentration of >10⁵ viable cells/mL. As a major consequence of this, many harmful or even pathogenic bacteria contained in some foods could survive the gastric transit and colonize either the stomach itself, the duodenum, or the gut, where they could establish acute and even chronic infections with unavoidable consequences for the host's health. In other words, the "gastric barrier effect" is strongly reduced or even disrupted. To date, there are no real strategies to deal with this widespread, although still relatively little known, problem. The aim of this study was to confirm the gastric bacterial overgrowth in long-term PPI consumers and to assess the efficacy of some probiotic bacteria, belonging to both genera Lactobacillus and Bifidobacterium, in the reduction of gastric and duodenal bacterial overgrowth, therefore partially restoring the gastric barrier effect against foodborne pathogenic bacteria. For this purpose, probiotics with a strong demonstrated inhibitory activity on gram-negative bacteria, such as Escherichia coli, were tested in a human intervention trial involving a total of 30 subjects treated with PPIs for either 3 to 12 consecutive months (short-term) or >12 consecutive months (long-term). An additional 10 subjects not taking PPIs were enrolled and used as a control group representing the general population. Four selected probiotics Probiotical SpA (Novara, Italy), namely Lactobacillus rhamnosus LR06 (DSM 21981), Lactobacillus pentosus LPS01 (DSM 21980), Lactobacillus plantarum LP01 (LMG P-21021), and Lactobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106) were administered for 10 days to 10 subjects treated with PPIs for >12 months (group B). In the 60 mg formulation, N-acetylcysteine was included as well in light of its well-known mechanical effects on bacterial biofilms. Gastroscopies were performed at the beginning of the study (d0) in all the groups (A, B, C, and D) and after 10 days (d10) in group B only; that is, at the end of probiotics intake. The total viable cells and total Lactobacillus were quantified in gastric juice and duodenal brushing material from all subjects. The results were compared among all the groups and with the control subjects (group D) to confirm the bacterial overgrowth. A comparison was made also between d0 and d10 in group B to quantify the efficacy of the 4 probiotics administered for 10 days. Fecal samples were collected from all groups at d0, including subjects not treated with PPIs, and in group B only at d10. Specific bacterial classes, namely enterococci, total coliforms, E. coli, molds, and yeasts were quantified in all fecal specimens. The results collected confirmed the strong bacterial overgrowth in the stomach and duodenum of people treated with PPIs compared with subjects with a normal intragastric acidity. It is also worth noting that the bacterial cell counts in subjects who underwent a long-term treatment with a PPI were greater than the results from subjects taking these drugs for 3 to 12 months. The intake of 4 specific probiotic strains with a marked antagonistic activity towards 5 E. coli bacteria, including the enterohaemorrhagic O157:H7 strain, and an effective amount of N-acetylcysteine (NAC) was able to significantly reduce bacterial overgrowth in long-term PPI-treated subjects. Total lactobacilli represented the major percentage of bacterial counts, thus demonstrating the ability of such bacteria to colonize the stomach and the duodenum, at least temporarily, and to consequently restore the gastric barrier effect. A significant decrease in fecal enterococci, total coliforms, E. coli, molds, and yeasts in subjects treated with PPIs was recorded at the end of probiotics supplementation (d10) compared with baseline (d0) in group B. This is a further confirmation of the barrier effect also exerted at the stomach level. PPIs are the most widely sold and used drugs in the world. However, the chronic use of these pharmacological molecules exposes the subject to the risk of foodborne infections as most pathogens are able to survive the gastric transit in a condition of significantly decreased acidity.

Intragastric acidity during the first day following administration of low-dose proton pump inhibitors: A randomized crossover study

Low-dose proton pump inhibitors (PPIs) are often administrated as maintenance therapy for gastroesophageal reflux disease (GERD) and on-demand PPI therapy is a viable option for long-term management of GERD. The aim of this study is to investigate intragastric acidity during the first day following the administration of low-dose PPIs. The study employed a crossover design. The subjects were 10 healthy volunteers who were administrated lansoprazole 15 mg (orally disintegrating) or rabeprazole 10mg. All subjects underwent pH monitoring with a wireless system during the first day after PPI administration. There was no significant difference in the average intragastric pH during the first day of administration of lansoprazole and rabeprazole (3.3±1.1 vs. 3.2±0.7, paired t test), although the pH was significantly higher with both drugs as compared with the baseline (1.8±0.4, P<0.01). The pH 4 holding time ratio during the first day showed no significant difference between lansoprazole and rabeprazole (35.2±22.4% vs. 34.3±15.0%), and was also significantly higher than at baseline (0.35±1.73%, P<0.01). The two PPIs differed with respect to the peak of the pH 4 holding time ratio. Lansoprazole 15 mg and rabeprazole 10 mg showed sufficient inhibition of intragastric acidity during the first day after PPI administration and the effects did not differ between drugs, although there was a difference in their time at which the peak effects were reached.

Rabeprazole 10 mg q.d.s. decreases 24‐h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype

Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid-related diseases. To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype. Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night-time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.

Evaluation of Potential Interactions between Mycophenolic Acid Derivatives and Proton Pump Inhibitors

To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity does not impact EC-MPA and bioavailability is maintained with this formulation during PPI coadministration. The clinical impact of this interaction is unknown, yet one can theorize that reduced exposure to MPA in SOT recipients can increase the risk of allograft rejection and/or failure.

Traditional vs wireless intragastric pH monitoring: are the two techniques comparable?

Few data are available comparing intragastric pH measured with the traditional catheter-based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points. Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo-columnar junction (SCJ) and of a dual-electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ. The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001). (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

Background and aims. Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Inhibitory effects of intravenous lansoprazole 30 mg and pantoprazole 40 mg twice daily on intragastric acidity in healthy Chinese volunteers: A randomized, open-labeled, two-way crossover study

SummaryBackgroundUntil now there has been no study that directly compares the effect of lansoprazole and pantoprazole administered intravenously on intragastric acidity. The aim of this study is to compare the effect of lansoprazole (30 mg) and pantoprazole (40 mg) administered intravenously on gastric acidity.Material/MethodsHelicobacter pylori-negative healthy volunteers were recruited in this open-label, randomized, two-way crossover, single centre study. Lansoprazole at 30 mg or pantoprazole at 40 mg was intravenously administered twice daily for 5 consecutive days with at least a 14-day washout interval. Twenty-four-hour intragastric pH was continuously monitored on days 1 and 5 of each dosing period.ResultsTwenty-five volunteers completed the 2 dosing periods. The mean intragastric pH values were higher in subjects treated with lansoprazole than those with pantoprazole on both day 1 (6.41±0.14 vs. 5.49±0.13, P=0.0003) and day 5 (7.09±0.07 vs. 6.64±0.07, P=0.0002). Significantly higher percentages of time with intragastric pH >4 and pH >6 were found in the subjects treated with lansoprazole than those with pantoprazole on day 1 (pH >4, 87.12±4.55% vs. 62.28±4.15%, P=0.0012; pH >6, 62.12±4.12% vs. 47.25±3.76%, P=0.0216) and pH >6 on day 5 (76.79±3.77% vs. 58.20±3.77%, P=0.0025).ConclusionsIntravenous lansoprazole produces a longer and more potent inhibitory effect on intragastric acidity than does intravenous pantoprazole.

Effect of Intravenous Esomeprazole 40 mg and Pantoprazole 40 mg on Intragastric pH in Healthy Subjects

<i>Objective</i>: The aim of this study was to compare the effect on intragastric acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.) esomepra-zole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40 mg (CAS for pantoprazole sodium: 138786-67-1). <i>Methods</i>: In an open, randomised, two-way cross-over study, 36 healthy volunteers received esomeprazole (Nexium^®) 40 mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection for 3 consecutive days. Continuous 24-h pH recordings were made under standardised conditions at baseline and on days 1 and 3 of each treatment period. The primary variable was the percentage of time with intragastric pH > 4 during a 24-h period. <i>Results</i>: Time with intragastric pH > 4 was significantly greater with esomeprazole than with pantoprazole during the first 4 h (47.8 % vs. 18.9 %), as well as for the 24-h period of day 1 and day 3 (day 1: 38.8 % vs. 23.7 %; day 3: 55.0 % vs. 35.2 %, p<0.0001 for all times examined). Mean of median intragastric pH with esome-prazole was significantly higher than with pantoprazole during the 24-h period (day 1: 3.2 vs. 2.2, p<0.0001; day 3: 4.3 vs. 3.1, p<0.00001). <i>Conclusion</i>: Esomeprazole administered as a 40 mg i.v. bolus injection provided faster and more effective control of intra-gastric acidity than a 40 mg i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of dosing.

Disease Characteristics in Non-Erosive Reflux Disease with and without Endoscopically Minimal Change Esophagitis: Are They Different?

Background/Aims: The majority of patients with gastroesophageal reflux disease (GERD) appear to have non-erosive reflux disease (NERD). NERD may include minimal change esophagitis (MCE) and no endoscopic abnormalities (MCE–). We aimed to determine whether intraesophageal acid reflux as well as esophageal motility differed between patients with and without MCE. Methods: Consecutive patients with classic reflux symptoms were enrolled in the study. Patients without any mucosal injury were considered to be MCE–. Esophageal acid exposure as well as intragastric pH (<4) was determined by dual-channel ambulatory 24-hour pH monitoring. Results: A total of 100 patients (MCE–, 52 patients; MCE, 48 patients) were studied. The percentage of effective peristalsis was found similar between patients with and without MCE (p = NS). Esophageal acid contact as well as the DeMeester score did not differ between the groups (p = NS). The prevalence of positive symptom index was greater in MCE– patients than in MCE patients (p = 0.001). Intragastric acidity (pH <4) was similar between MCE– and MCE groups (p = NS). Conclusions: NERD, regardless of the presence of MCE, might exhibit similar disease characteristics in terms of esophageal acid exposure and motor dysfunction.

Intragastric acidity during administration of generic omeprazole or esomeprazole - a randomised, two-way crossover study including CYP2C19 genotyping

Generic omeprazole has been approved in many countries for the treatment of acid-related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited. To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status. In this randomised, single-blinded, two-way crossover study, 24 healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively]. Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.

This Month in Gastroenterology

This Month in Gastroenterology