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Acid Suppression (acid + suppression)
Kinds of Acid Suppression Selected AbstractsSystematic review: impaired drug absorption related to the co-administration of antisecretory therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009E. LAHNER Summary Background, Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur. Aim, To review evidence of impaired drug absorption related to the use of co-administered PPIs or H2RAs. Methods, Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980,September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti-secretory/acid inhibitory drugs, histamine H2 antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co-administration of PPIs or H2RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted. Results, The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median Cmax reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed. Conclusions, Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co-administered drugs. [source] Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005A prospective, randomized clinicopharmacological study Summary Background:, Acid suppression plus two antibiotics is currently considered the gold standard anti- Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. Aims:, To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. Methods:, A total of 150 dyspeptic H. pylori -infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. Results:, On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). Conclusion:, Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens. [source] Doxycycline-induced pill esophagitisDISEASES OF THE ESOPHAGUS, Issue 2 2004A. Kadayifci SUMMARY., Pill-induced esophagitis is a complication seen in patients who use certain medications such as tetracycline and non-steroidal anti-inflammatory drugs. In this short report, we described five cases of doxycycline-induced esophagitis with endoscopic images. All of the patients were young or middle-aged women. Dysphagia or odynophagia with retrosternal pain were the main presenting symptoms in all cases. The observed injuries were at the middle third of esophagus with a normal surrounding mucosa. All patients had a history of swallowing the capsule with a small amount of water or in a recumbent position. Two patients with dysphagia were managed by intravenous fluid support and parenteral acid suppression. The symptoms were improved in 2,7 days after the ceasing of the drug and control endoscopies were completely normal in all cases after 3,4 weeks of admission. The drug-induced esophagitis is not rare with certain drugs and should be suspected in all patients presenting with chest pain and dysphagia. Physicians must warn the patients to take the pills and capsules with enough liquid and in the upright position. [source] Impact of Furazolidone-Based Quadruple Therapy for Eradication of Helicobacter pylori after Previous Treatment FailuresHELICOBACTER, Issue 4 2002G. Treiber Abstract Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third-line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin-metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI-B-T-M) three times a day (tid) for 1 week. In the case of treatment failure with this second-line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI-B-T-F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI-B-T-M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI-B-T-F. Final cure of H. pylori with PPI-B-T-F was achieved in 9/10 patients (90%) nonresponsive to PPI-B-T-M. Conclusions. In the presence of metronidazole resistance, PPI-B-T-M as a recommended second-line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second-line quadruple therapy may be best suited in case of a metronidazole-free first line-regimen (e.g. PPI-clarithromycin-amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI-B-T-F combination does not have a cross-resistance potential to metronidazole and is a promising salvage option after a failed PPI-B-T-M regimen. [source] Is Eradication of Helicobacter pylori With Colloidal Bismuth Subcitrate Quadruple Therapy Safe?HELICOBACTER, Issue 2 2001Rosemary H. Phillips ABSTRACT Background. When standard triple therapy fails to eradicate Helicobacter pylori, quadruple ,rescue' therapy is often used which, in Europe, generally comprises colloidal bismuth subcitrate (CBS) based triple therapy and a proton pump inhibitor. Since hypochlorhydria could greatly increase absorption of the toxic bismuth ion from CBS, we investigated the bismuth status of patients receiving anti- H. pylori quadruple therapy. Materials and Methods. In a prospective open label study 34 patients with nonulcer dyspepsia or peptic ulcer disease, who had failed to eradicate H. pylori with standard triple therapy, were subsequently treated with CBS, omeprazole, amoxycillin and metronidazole (BOAM). A further 35 patients received triple therapy for the eradication of H. pylori: CBS, amoxycillin and metronidazole (BAM) (n = 18); placebo bismuth, amoxycillin and metronidazole (AM) (n = 9); or omeprazole, amoxycillin and metronidazole (OAM) (n = 8). Whole blood bismuth levels were determined before and within 24 hours of completing treatment. Analysis of bismuth was by inductively coupled plasma mass spectrometry, and concentrations were compared between groups and with the Hillemand ,alarm level' for blood bismuth (50,100 µg/l). Results. BOAM gave higher blood bismuth levels than BAM (difference in means 13.1, CI 6.0,20.2, p < .001); three (8.8%) patients taking BOAM had concentrations within the Hillemand alarm level at 54.2, 64.7 and 91.8 µg/l. OAM and AM did not alter baseline blood bismuth levels. Conclusions. Caution should be observed in prescribing CBS with gastric acid suppression, and alternative bismuth preparations should be considered. [source] Non-cardiac chest pain: Prevalence of reflux disease and response to acid suppression in an Asian populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2009Hanizam Mohd Abstract Background:, Gastroesophageal reflux disease is thought to be the commonest cause of ,non-cardiac chest pain'. The use of proton-pump inhibitors resulting in improvement in the chest pain symptom would support this causal association. Objectives:, To determine the prevalence of gastroesophageal reflux disease in non-cardiac chest pain and the response of chest pain to proton-pump inhibitor therapy. Methods:, Patients with recurrent angina-like chest pain and normal coronary angiogram were recruited. The frequency and severity of chest pain were recorded. All patients underwent esophagogastroduodenoscopy and 48-h Bravo ambulatory pH monitoring before receiving rabeprazole 20 mg bd for 2 weeks. Results:, The prevalence of gastroesophageal reflux disease was 66.7% (18/27). The improvement in chest pain score was significantly higher in reflux compared to non-reflux patients (P = 0.006). The proportion of patients with complete or marked/moderate improvement in chest pain symptoms were significantly higher in patients with reflux (15/18, 83.3%) compared to those without (1/9, 11.1%) (P < 0.001). Conclusion:, The prevalence of gastroesophageal reflux disease in patients with ,non-cardiac chest pain' was high. The response to treatment with proton-pump inhibitors in patients with reflux disease, but not in those without, underlined the critical role of acid reflux in a subset of patients with ,non-cardiac chest pain'. [source] Vitamin C inhibits corpus gastritis in Helicobacter pylori -infected patients during acid-suppressive therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Masahiro Yoshinaga Abstract Background: Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori) -positive patients. We evaluated the effect of acid-suppressive therapy and vitamin C on H. pylori -associated gastritis. Methods: Forty patients with reflux esophagitis were divided into three groups by the status of H. pylori and therapy: group A (n = 15), H. pylori (+) and omeprazole 20 mg; group B (n = 15), H. pylori (+) and omeprazole 20 mg + vitamin C 1200 mg; and group C (n = 10), H. pylori (,) and omeprazole 20 mg. In all three groups, the mucosal interleukin (IL)-8 contents, H. pylori colonization density, neutrophil infiltration in the corpus, and serum gastrin were evaluated at entry and 2 weeks after starting therapy; in group B, serum vitamin C levels were also measured. Results: In group A, the IL-8 contents and the degree of neutrophil infiltration during therapy exceeded those at entry, whereas in groups B and C, these values did not change significantly with treatment. Helicobacter pylori colonization density during therapy was similar to that at entry in all three groups. The serum gastrin (in all groups) and vitamin C levels (in group B) during therapy exceeded those at entry. Conclusions: Potent acid suppression worsens H. pylori -associated corpus gastritis, although such worsening gastritis may be inhibited by vitamin C. [source] The effects of high-dose esomeprazole on gastric and oesophageal acid exposure and molecular markers in Barrett's oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. Abu-Sneineh Aliment Pharmacol Ther 2010; 32: 1023,1030 Summary Background, Acid reflux is often difficult to control medically. Aim, To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). Methods, Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. Results, At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. Conclusions, High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation. [source] Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro-oesophageal reflux disease , comparator study of esomeprazole, lansoprazole and pantoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010D. Morgan Aliment Pharmacol Ther 2010; 32: 200,208 Summary Background, Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population. Aim, To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the ,acid pocket,' in Hispanics with GERD. Methods, In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5,7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10,17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the ,acid pocket') electrode. Results, Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001). Conclusions, Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592). [source] The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a Dual Delayed Release proton pump inhibitorALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010R. D. LEE Aliment Pharmacol Ther,31, 1001,1011 Summary Background, Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression. Aim, To evaluate the pharmacokinetics and pharmacodynamics of dexlansoprazole MR dosed before 4 different meal times. Methods, In this randomized, open-label, four-way crossover study, 48 healthy subjects received dexlansoprazole MR 60 mg once daily 30 min before breakfast, lunch, dinner or an evening snack. Pharmacokinetics of dexlansoprazole MR and intragastric pH were assessed over a 24-h postdose interval on day 5 for each regimen. Results, Absorption was delayed when dexlansoprazole MR was administered before each regimen relative to breakfast; however, systemic exposures of dexlansoprazole at all regimens were bioequivalent. There were no statistically significant differences in mean 24-h intragastric pH between dosing before dinner or an evening snack vs. breakfast; however, there was a small (0.2), but statistically significant difference between lunch and breakfast. There was a statistically significant difference of 7 percentage points in the percentage of time intragastric pH was >4 for the snack regimen relative to the breakfast regimen, but there were no statistically significant differences between lunch or dinner compared with breakfast. Conclusion, Dexlansoprazole MR provides comparable acid control when administered at different times of the day. [source] Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over-the-counter doses of proton pump inhibitorsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010P. B. MINER JR Aliment Pharmacol Ther,31, 846,851 Summary Background, Over-the-counter (OTC) proton pump inhibitors (PPIs) relieve heartburn by decreasing the production of gastric acid, but may not do so with equal effectiveness. It is important for healthcare professionals to compare the ability of OTC PPIs to control gastric acid when recommending them for patients with frequent heartburn. Aim, To compare the effects of omeprazole-Mg 20.6 mg and lansoprazole 15 mg (OTC doses in the US) on 24-h steady state gastric acid suppression. Methods, This single-centre, randomized, double-blind clinical study compared the steady-state gastric acid control of omeprazole-Mg 20.6 mg vs. lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3-period, cross-over design (ABB, BAA) with 24-h gastric pH monitoring on dosing day 5. The primary efficacy variable was the percentage time intragastric pH was >4.0 over 24 h on day 5 of dosing. Results, Forty subjects were enrolled; all completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%) for omeprazole-Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs were well tolerated. Conclusion, Omeprazole-Mg 20.6 mg provided a statistically significantly (P < 0.0001) greater acid control than lansoprazole 15 mg. [source] The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010R. H. HUNT Aliment Pharmacol Ther,31, 648,657 Summary Background, Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day. Aim, To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole. Methods, A single-centre, double-blind, double-dummy, randomized, 4-way, cross-over study was conducted in 32 healthy male subjects. S-tenatoprazole-Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10-day washout intervals. The 24-h intragastric pH was recorded at baseline and on day 5 of each period. Results, On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24-h were higher with S-tenatoprazole-Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S-tenatoprazole-Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S-tenatoprazole-Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S-tenatoprazole-Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02). Conclusions, S-tenatoprazole-Na produced significantly greater and more prolonged dose-dependent 24-h and nocturnal acid suppression than esomeprazole. S-tenatoprazole-Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once-daily therapy. [source] Clinical trial: long-term use of proton pump inhibitors in primary care patients , a cross sectional analysis of 901 patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009C. REIMER Summary Background, The use of proton pump inhibitors (PPIs) is extensive. While the incidence of new treatments remains stable, the prevalence of long-term treatment is rising. Studies have shown that up to 70% of patients on chronic acid suppression lack a verified indication for treatment. Aims, To investigate primary care patient characteristics associated with long-term use of PPIs. Methods, A cross-sectional analysis of 42 634 patients registered with 22 general practitioners was performed. Patients with prescriptions of ,120 tablets/year were defined as long-term users. A survey of a subgroup of patients without verified indication was performed. Results, In all, 901 (2.1%) patients were long-term treated. Verified indications for treatment were identified for 247/901 (27%). An upper GI endoscopy had been performed in 418 patients (46%). Of the 194/654 without verified indication who participated in the survey, 71% reported heartburn/acid regurgitation as the reason for therapy. On-demand therapy was reported by 43/194 (22%) and previous attempts to withdraw by 119/194 (61%). Conclusions, The prevalence of PPI long-term treatment among primary care patients is 2.1%. The main reason for treatment is reflux symptoms or verified GERD. Rationalization of use of PPIs is possible as daily treatment without attempts to discontinue is frequently observed. [source] Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009D. C. METZ Summary Background, Proton pump inhibitors (PPIs) provide the most effective pharmacotherapy for treating acid-related disorders. However, PPIs do not completely control acid over 24 h with once-daily dosing. Aims, To discuss limitations inherent in the pharmacokinetics (PK) and pharmacodynamics of conventional PPI formulations, which provide a single drug release. Also, to consider approaches to extending the duration of acid suppression focusing on dexlansoprazole MR, a PPI with a novel Dual Delayed Release (DDR) formulation. Method, We reviewed the available literature regarding marketed and investigational PPIs. Results, Non-standard dosing of currently marketed PPIs has produced incremental advances in acid control. Multiple approaches are being evaluated to enhance acid suppression with PPIs. Dexlansoprazole MR is a DDR formulation of dexlansoprazole, an enantiomer of lansoprazole, with two distinct drug release periods to prolong the plasma dexlansoprazole concentration,time profile and extend duration of acid suppression. Clinical studies show that dexlansoprazole MR produces a dual-peak PK profile that maintains therapeutic plasma drug concentrations longer than lansoprazole, with a single-peak PK profile, and increases the percentage of time that intragastric pH >4. Conclusions, Novel drug delivery platforms, including the dexlansoprazole MR DDR formulation, may improve acid suppression and offer benefits over conventional single release PPI formulations. [source] Clinical trial: a randomized trial of early endoscopy, Helicobacter pylori testing and empirical therapy for the management of dyspepsia in primary careALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009A. E. DUGGAN Summary Background, Early endoscopy, Helicobacter pylori eradication and empirical acid suppression are commonly used dyspepsia management strategies in primary care but have not been directly compared in a single trial. Aim, To compare endoscopy, H. pylori test and refer, H. pylori test and treat and empirical acid suppression for dyspepsia in primary care. Methods, Patients presenting to their general practitioner with dyspepsia were randomized to endoscopy, H. pylori,test and treat', H. pylori test and endoscope positives, or empirical therapy with symptoms, patient satisfaction, healthcare costs and cost effectiveness at 12 months being the outcomes. Results, At 2 months, the proportion of patients reporting no or minimal dyspeptic symptoms ranged from 74% for those having early endoscopy to 55% for those on empirical therapy (P = 0.009), but at 1 year, there was little difference among the four strategies. Early endoscopy was associated with fewer subsequent consultations for dyspepsia (P = 0.003). ,Test and treat' resulted in fewer endoscopies overall and was most cost-effective over a range of cost assumptions. Empirical therapy resulted in the lowest initial costs, but the highest rate of subsequent endoscopy. Gastro-oesophageal cancers were found in four patients randomized to the H. pylori testing strategies. Conclusions, While early endoscopy offered some advantages ,Test and treat' was the most cost-effective strategy. In older patients, early endoscopy may be an appropriate strategy in view of the greater risk of malignant disease. [source] Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis , a randomized controlled, cross-over trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007P. JANIAK Summary Background, Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. Aim, To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. Methods, Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. Results, Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. Conclusion, Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population. [source] Long-term use of proton pump inhibitors does not affect the frequency, growth, or histologic characteristics of colon adenomasALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2007M. SINGH Summary Background, The clinical significance of the trophic effects of long-term proton pump inhibitors (PPI)-related hypergastrinemia on colon polyps remains unknown. Aim, To study the frequency, growth, and histology of colon polyps in patients on chronic PPI therapy (cases), compared to those not receiving acid suppression (controls). Methods, Medical records of 2868 consecutive patients who underwent two or more colonoscopies, performed 3 or more months apart were reviewed. Cases (116) that used PPIs between the two colonoscopies were then compared to controls (194). Results, Demographics and risk factors for colon cancer were comparable between the two groups. At baseline the mean frequency and size of adenomatous polyps were similar in cases and controls (P > 0.05) and at follow-up, these were 0.89 and 1.18 (P > 0.05; 95% CI of ,0.08 to 0.66) and 4.09 mm and 4.00 mm (P > 0.05; 95% CI ,2.29 to 2.11), respectively with no significant change. However, control group had a higher mean frequency and size of hyperplastic polyps at baseline as well as at follow-up colonoscopy (P < 0.05). Conclusions, The long-term use of PPI does not influence the frequency, growth, or histology of adenomatous polyps, but is associated with a reduction in both baseline and interval development of hyperplastic polyps. [source] Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2007C. J. PETERS Summary Background Oesophageal adenocarcinoma is an increasingly common cancer with a poor prognosis. It develops in a stepwise progression from Barrett's metaplasia to dysplasia, and then adenocarcinoma followed by metastasis. Aim To outline the key molecular changes in oesophageal adenocarcinoma and to summarize the chemopreventative and therapeutic strategies proposed. Methods A literature search was performed to identify appropriate research papers in the field. Search terms included: Barrett's (o)esophagus, intestinal metaplasia, (o)esophageal adenocarcinoma, molecular changes, genetic changes, pathogenesis, chemoprevention, therapeutic strategies and treatment. The search was restricted to English language articles. Results A large number of molecular changes have been identified in the progression from Barrett's oesophagus to oesophageal adenocarcinoma although there does not appear to be an obligate order of events. Potential chemoprevention strategies include acid suppression, anti-inflammatory agents and antioxidants. In established adenocarcinoma, targeted treatments under evaluation include receptor tyrosine kinase inhibitors of EGFR and cyclin-dependent kinase inhibitors, which may benefit a subgroup of patients. Conclusions Advances in molecular methodology have led to a greater understanding of the oesophageal adenocarcinoma pathways, which provides opportunities for chemoprevention and therapeutic strategies with a mechanistic basis. More work is required to assess both the safety and efficacy of these new treatments. [source] Symptom overlap in patients with upper gastrointestinal complaints in the Canadian confirmatory acid suppression test (CAST) study: further psychometric validation of the reflux disease questionnaireALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007S. V. VAN ZANTEN Summary Background The reflux disease questionnaire (RDQ) is a short, patient-completed instrument. Aims To investigate the psychometric characteristics of the RDQ in patients with heartburn-predominant (HB) and non-heartburn predominant (NHB) dyspepsia. Methods HB (n = 388) and NHB (n = 733) patients were randomized to esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of esomeprazole 40 mg daily. Results High factor loadings (0.78,0.86) supported the ,regurgitation' dimension of the RDQ. Overlapping factor loadings in the ,heartburn' and ,dyspepsia' dimensions suggested symptom overlap. All dimensions demonstrated high internal consistency (Cronbach's alpha: 0.79,0.90). Intra-class correlation coefficients over 4 weeks were good (0.66,0.85). The RDQ showed good responsiveness over 4 weeks of treatment, with high effect sizes (,0.80). Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB patients, respectively, following treatment. Patients who responded to acid suppression also experienced symptom benefits in all RDQ dimensions. Conclusions The RDQ is reliable, valid and responsive to change in HB and NHB patients. The symptom overlap is important but need not play a major role in determining treatment strategy as both patient groups benefited from proton pump inhibitor treatment. [source] Oral rabeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007D. ARMSTRONG Summary Background Intravenous pantoprazole is often administered inappropriately to hospitalized patients who can take oral medications. Aim To compare the antisecretory effects of oral rabeprazole and intravenous pantoprazole in healthy subjects. Methods In a double-blind, double-dummy, two-way crossover study, 38 Helicobacter pylori -negative volunteers were randomized to oral rabeprazole 20 mg or intravenous pantoprazole 40 mg daily for 3 days followed, after a 14-day washout period by the comparator treatment. Intragastric pH was recorded continuously for 24 h at baseline and on days 1 and 3 of each treatment period. Results The mean (95% CI) percentage of the 24-h recording with gastric pH >4 was higher with rabeprazole than with pantoprazole on day 1: 37.7% (30.6,44.8%) vs. 23.9% (20.0,27.8). The mean percentage times with pH >3 and >4 for all intervals assessed were greater and the median 24-h intragastric pH values were higher with rabeprazole than with pantoprazole on days 1 and 3. The mean acidity index was lower with rabeprazole on days 1 and 3. Conclusions Oral rabeprazole 20 mg produced greater acid suppression than intravenous pantoprazole 40 mg. Therefore, it may be an appropriate and effective alternative in patients who can take oral medication. [source] Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006A. B. R. THOMSON Background, The effectiveness of proton pump inhibitors is influenced by meals and administration time. Aim, To compare the effects on intragastric acidity of times of dosing of tenatoprazole, a novel imidazopyridine-based proton pump inhibitor with a prolonged plasma half-life. Methods, This randomized three-period crossover study included 12 Helicobacter pylori -negative healthy subjects, who received tenatoprazole 40 mg either fasting at 7.00 am, fasting at 7.00 pm or fed at 9.30 pm for 7 days, with a 2-week washout between periods. Twenty-four hour intragastric pH was monitored on day 7 of each period. Results, On day 7, median 24-h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing, respectively (P = 0.11), whereas night-time pH was 4.2, 5.0 and 4.4 (P = 0.13). The mean 24-h percentage of time over pH 4 was 62, 72 and 64 after breakfast, dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night-time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at baseline to 83%, 55% and 75% after 7.00 am, 7.00 pm and 9.30 pm dosing, respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and 2.2 h, respectively (P < 0.05). Conclusion, Seven-day administration of tenatoprazole provides a prolonged duration of acid suppression, especially during the night-time, with little effect of food or time of dosing. [source] Review article: From gastrin to gastro-oesophageal reflux disease , a century of acid suppressionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006P. MALFERTHEINER Summary To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century. [source] Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006L. LUNDELL Summary Background, The impact of long-term acid suppression on the gastric mucosa remains controversial. Aim, To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up. Methods, Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. Results, Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. Conclusions, Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori -negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori -positive patients there are changes in mucosal inflammation and atrophy. [source] The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal refluxALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2005W. C. Orr Summary Background :,Several studies have demonstrated that night-time gastro-oesophageal reflux affects sleep quality, and thereby impairs daytime functioning. Aim :,To determine whether treatment with a proton-pump inhibitor (rabeprazole) would improve both objective and subjective measures of sleep. Methods :,Individuals with complaints of significant gastro-oesophageal reflux disease were studied by polysomnography and 24-h pH monitoring on two separate nights. On one occasion, participants received 20 mg rabeprazole b.d., and on another they received placebo. Both study conditions were preceded by a week of treatment with either rabeprazole or placebo. The order of treatments was randomized. Results :,Rabeprazole significantly reduced overall acid reflux, but it did not significantly reduce night-time acid contact. Rabeprazole treatment significantly improved subjective indices of sleep quality. There were no significant differences on objective measures of sleep between placebo and rabeprazole treatment. Conclusions :,Consistent with other studies of pharmacological treatments for gastro-oesophageal reflux, subjective measures of sleep improved with heartburn medication but objective measures were not affected. [source] Effect of low-dose rabeprazole and omeprazole on gastric acidity: results of a double blind, randomized, placebo-controlled, three-way crossover study in healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004S. Bruley des Varannes Summary Background :,The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens. Aim :,To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori -negative subjects. Methods :,In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10,14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment. Results :,Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo). Time with gastric pH above 4 was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs. 3.7 h, respectively (P < 0.02); day 7, 10.5 h vs. 4.6 h, respectively (P = 0.0008). Conclusions :,Rabeprazole 10 mg provides more rapid acid inhibition compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more than doubled with rabeprazole 10 mg vs. omeprazole 10 mg. [source] Double gastric infection with Helicobacter pylori and non- Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2001S. Sanduleanu Background: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori -positive subjects. The pathogenetic mechanism remains unclear. Aim: To test the hypothesis that gastric double infection with H. pylori and non -H. pylori bacterial species,during acid suppression,may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. Patients and methods: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2 -receptor antagonists (H2 -RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non- H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1,, IL-6, and IL-8 were examined. Results: Patients on acid suppression with either proton pump inhibitors or H2 -RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non- H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non- H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non- H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1, and IL-8). Summary and conclusions: H. pylori -positive patients on long-term acid inhibition displayed three features: non- H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non- H. pyloribacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition. [source] Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mgALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001P. O. Katz Background: Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity. Aim: To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control. Methods: Study I: 12 Helicobacter pylori -negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24-h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean ± s.d. Results: (1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night-time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 ± 19% vs. 48 ± 14%, P < 0.001), and night-time periods (34 ± 21% vs. 26 ± 14%, P < 0.05). (3) A large inter-subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 ± 18% vs. 51 ± 15%, P=0.015) than omeprazole 20 mg. Conclusion: These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole. [source] Barrett's oesophagus, dysplasia and pharmacologic acid suppressionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2001R. C. Fitzgerald Barrett's oesophagus, a significant complication of gastro-oesophageal reflux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett's oesophagus and chronic GERD suggests that abnormal oesophageal acid exposure plays an important role in this condition. The progression of Barrett's oesophagus from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of acid, whilst proliferation is reduced in Barrett's oesophagus specimens taken from patients with oesophageal acid exposure normalized by antisecretory therapy. In long-term clinical studies, consistent and profound intra-oesophageal acid suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical importance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal acid exposure and the risk for dysplasia or adenocarcinoma persist in many patients. The ability of proton pump inhibitors to suppress acid profoundly and consistently may be critical in the long-term management of Barrett's oesophagus. [source] Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitorsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000Laine This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger,Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression. [source] H+/K+ -ATPase (proton pump) inhibitors dampen increased cough reflex: more than gastric acid suppressionCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2005K. F. Chung No abstract is available for this article. [source] | ||||||||||