Lansoprazole in the treatment of gastrooesophageal reflux disease in childhood

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.     

不同质子泵抑制剂三联治疗幽门螺杆菌阳性糜烂性胃炎的疗效差异

目的 比较不同质子泵抑制剂(PPI)和抗生素三联疗法治疗幽门螺杆菌(Hp)阳性糜烂性胃炎的疗效差异.方法 将Hp阳性糜烂性胃炎545例随机给予奥美拉唑、埃索美拉唑、泮托拉唑、兰索拉唑或雷贝拉唑联合阿莫西林与克拉霉素三联疗法治疗7d,比较各组疗效差异.结果 埃索美拉唑组在缓解症状、改善胃镜下表现方面显著高于其它各组,雷贝...     

Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician

The suppression of gastric acid secretion with anti-secretory agents has been the mainstay of medical treatment for patients with acid-related disorders. Although the majority of Helicobacter pylori -related peptic ulcers can be healed with antibiotics, ulcer healing and symptom control can be significantly improved when antibiotics are given with anti-secretory agents, especially with a proton pump inhibitor. There is a dynamic relationship between the suppression of intragastric acidity and the healing of peptic ulcer and erosive oesophagitis and control of acid-related symptoms. The suppression of gastric acid secretion achieved with H(2)-receptor antagonists has, however, proved to be suboptimal for effectively controlling acid-related disorders, especially for healing erosive oesophagitis and for the relief of reflux symptoms. H(2)-receptor antagonists are also not effective in inhibiting meal-stimulated acid secretion, which is required for managing patients with erosive oesophagitis. Furthermore, the rapid development of tolerance to H(2)-receptor antagonists and the rebound acid hypersecretion after the withdrawal of an H(2)-receptor antagonist further limit their clinical use. Although low-dose H(2)-receptor antagonists are currently available as over-the-counter medications for self-controlling acid-related symptoms, their pharmacology and pharmacodynamics have not been well studied, especially in the self-medicating population. Proton pump inhibitors have been proved to be very effective for suppressing intragastric acidity to all known stimuli, although variations exist in the rapidity of onset of action and the potency of acid inhibition after oral administration at the approved therapeutic doses, which may have important clinical implications for the treatment of gastro-oesophageal reflux disease and perhaps for eradicating H. pylori infection when a proton pump inhibitor is given with antibiotics. Once-daily dosing in the morning is more effective than dosing in the evening for all proton pump inhibitors with respect to the suppression of intragastric acidity and daytime gastric acid secretion in particular, which may result from a better bio-availability being achieved with the morning dose. When higher doses are needed, these drugs must be given twice daily to achieve the optimal suppression of 24 hour intragastric acidity. Preliminary results have shown that esomeprazole, the optical isomer of omeprazole, given at 40 mg, is significantly more effective than omeprazole 40 mg, lansoprazole 30 mg or pantoprazole 40 mg for suppressing gastric acid secretion. However, more studies in different patient populations are needed to compare esomeprazole with the existing proton pump inhibitors with regard to their efficacy, cost-effectiveness and long-term safety for the management of acid-related disorders.     

Evaluation of gastric acid secretion in two patients (each aged over 90 years) with <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-negative nonsteroidal anti-inflammatory drug-caused duodenal ulcers

We treated two patients (each aged over 90 years) with Helicobacter pylori-negative nonsteroidal anti-inflammatory drug (NSAID)-caused duodenal ulcers, and had the opportunity to determine gastric acidity by means of 24-h pH monitoring. Endoscopic and histological examination showed no remarkable atrophic change in the gastric mucosa. The gastric pH was low throughout the day and night, and the gastric pH ≧ 3 holding time ratio during 24 h was 17.1% and 25.8%, respectively in the two patients, so it was considered that they had gastric acid secretion of the same level as that in normal subjects of the same age or that in the young without H. pylori infection. Because of the complication of reflux esophagitis with a hiatal hernia, rabeprazole sodium, one of the proton pump inhibitors (PPIs), was administered and both patients made excellent progress. In conclusion, gastric acid secretion in patients with H. pylori-negative NSAID-caused duodenal ulcers is fully maintained even in the elderly, so PPIs may be the first choice of treatment. Received: March 27, 2001 / Accepted: December 27, 2001 Reprint requests to: T. Shimatani     

Control of intra-oesophageal and intra-gastric pH with proton pump inhibitors in patients with Barrett''s oesophagus

BACKGROUND: A significant percentage of patients with Barrett's oesophagus (BE) will continue to manifest abnormal intra-oesophageal pH profiles regardless of proton pump inhibitor (PPI) therapy. AIMS: We conducted a prospective study in order to determine whether a change in PPI therapy would alter intra-oesophageal and intra-gastric acid suppression in BE patients. PATIENTS: Seventeen Helicobacter pylori-negative BE patients (16 males, 1 female; mean+/-S.D. age, 63.5+/-13.2). METHODS: Twenty-four-hour pH monitoring was performed on omeprazole or lansoprazole, followed by repeat pH monitoring on rabeprazole at a dose titrated for symptom relief. Patients completed validated symptom and health-related quality-of-life (HRQL) surveys while on and off therapy. RESULTS: Ten (59%) of the 17 patients had abnormal baseline intra-oesophageal pH profiles. Oesophageal pH monitoring values on rabeprazole were abnormal in five out of five (100%) of the omeprazole cohort and three out of five (60%) of the lansoprazole cohort that had abnormal pH profiles on initial testing. Intra-gastric pH control was inadequate in BE patients on all PPIs; the mean percentage time with intra-gastric pH below 4.0 was 46% on omeprazole, 71% on lansoprazole and 51% on rabeprazole (p=0.25). All of the patients demonstrated the phenomenon of nocturnal acid breakthrough while undergoing PPI therapy. CONCLUSIONS: Change in PPI therapy did not alter intra-oesophageal or intra-gastric control in patients with BE.     

Influence of acid suppressants on gastric emptying: cross-over analysis in healthy volunteers

BACKGROUND: Gastric emptying plays an important role in gastroesophageal reflux disease. Acid suppressants such as H2 receptor antagonists and/or proton pump inhibitors are often used in patients with gastroesophageal reflux disease. However, it remains controversial whether H2 receptor antagonists and proton pump inhibitors delay or accelerate gastric emptying. Here, the influence of acid suppressants on gastric emptying was evaluated via a cross-over study using the [13C]-labeled acetate breath test. METHODS: Twenty normal male subjects without gastroesophageal reflux disease symptoms were enrolled. Gastric emptying was investigated five times in every subject by the [13C]-labeled acetate breath test with oral administration of the vehicle, domperidone, and three acid suppressants: ranitidine, famotidine and rabeprazole. Gastric emptying was estimated by the values of T(max-calc), T(1/2) and %dose/2 h calculated from the 13CO2 breath excretion curve. RESULTS: Using the T(max-calc) values, rabeprazole, ranitidine and famotidine did not influence gastric emptying time in comparison with vehicle administration. Using the T(1/2) and %dose/2 h values, rabeprazole tended to delay gastric emptying. Domperidone produced a statistically significant acceleration of gastric emptying for all three variables (P < 0.05). CONCLUSION: Oral dosage of the H2 receptor antagonists, ranitidine and famotidine, has no significant effect on gastric emptying. However, rabeprazole may delay gastric emptying more strongly than H2 receptor antagonists.     

Effect of pantoprazole versus other proton pump inhibitors on 24-hour intragastric pH and basal acid output in Zollinger-Ellison syndrome

AIM: In this open prospective study, the efficacy of pantoprazole in reducing gastric acid secretion in Zollinger-Ellison syndrome patients was compared to that obtained previously with other proton pump inhibitors.METHODS: Eleven male patients previously treated with omeprazole (n=7, mean dosage: 63 mg/day; range: 20-100 mg/day) or lansoprazole (n=4, mean dosage: 75 mg/day; range: 30-120 mg/day) were included. These patients underwent a 24-hour intragastric pH-metry, measurement of basal acid output and of serum gastrin first while receiving their usual therapy and second after 7 to 10 days of pantoprazole treatment at a mean dosage of 116 mg/day (range: 40-200 mg/day). Basal acid output was evaluated after each intragastric pH-metry, one hour before the next intake of proton pump inhibitor and a serum gastrin curve was determined according to 9 fixed time points.RESULTS: One patient dropped out before the second intragastric pH-metry due to an adverse event (varicella) unrelated to pantoprazole and was reinvestigated thereafter. The median 24-h intragastric pH with pantoprazole was not significantly different than that with the other proton pump inhibitors (5.3 versus 4.6, respectively; P=0.90). Neither the median basal acid output values nor the median serum gastrin levels were significantly different between pantoprazole and the other proton pump inhibitors.CONCLUSION: In these patients with the Zollinger-Ellison syndrome, pantoprazole was well tolerated and equally effective to the other proton pump inhibitors in terms of antisecretory potency.     

Control of intragastric pH and its relationship to gastroesophageal reflux disease outcomes

Pharmacologic treatment of gastroesophageal reflux disease (GERD) is accomplished almost exclusively with medications whose primary mechanism of action is to inhibit or neutralize gastric acidity, thus treating the disease by reducing exposure to the primary injurious agent and not by decreasing actual reflux. Although clinical trials assess healing of erosive esophagitis, improvement of GERD symptoms, and quality of life (the ultimate measures of therapeutic success), pharmacodynamic studies that measure gastric acid control have been used as 1 method of assessment of the potential clinical efficacy of acid suppressant medications. Continuous intragastric pH monitoring has been used extensively to evaluate therapeutic dosing for proton pump inhibitors and comparatively characterize their antisecretory efficacy. However, the link between observed changes in gastric pH and GERD outcomes is not well established. This review summarizes and critically evaluates available evidence linking intragastric pH and GERD outcomes. A search of the published literature for relevant studies, combined with the authors' knowledge of the field, revealed few studies that directly evaluated the correlation between intragastric pH and clinical outcomes. Despite the clinical relevance of heartburn and related symptoms as an outcome for GERD patients, most intragastric pH studies that did assess outcomes were limited in their evaluation of these symptoms because healing of erosions rather than symptom relief was specified as the primary endpoint. Well-designed, long-term outcome studies are still needed to elucidate the link among GERD symptoms, acid suppressive therapy, and 24-hour gastric pH profiles.     

The effect of H2-receptor antagonist and proton pump inhibitor on microbial proliferation in the stomach

BACKGROUND/AIMS: Intra-gastric bacterial proliferation is frequent in patients with hypochlohydria. However, status of gastric bacterial infection in patients receiving proton pump inhibitor or H2-receptor antagonist remains controversial. The purpose of this study was to investigate the microbial condition of the stomach in patients who received H2-receptor antagonist or proton pump inhibitor. METHODOLOGY: Between November 2000 and January 2002, 102 patients were enrolled in this study. Of these, 52 did not receive any treatment (group I), 26 received H2-receptor antagonist (group II), and 24 received proton pump inhibitor (group III). Ten mL of gastric juice were aspirated for culture during endoscopic examination. The aerobic and anaerobic bacterial and fungal cultures were performed immediately. A glass pH meter measured the pH of the gastric juice. RESULTS: The intra-gastric pH was 2.91+/-2.06 (mean +/- SD), 4.12+/-2.83, and 5.11+/-2.47 for groups I, II, and III, respectively (p=0.001 between groups I and III, p>0.05 between groups I and II, and groups II and III). The positive bacterial culture rates were 66.7% (16/24) in group III, 46.2% (12/26) in group II, and 28.8% (15/52) in group I (p=0.007 between groups III and I,p>0.05 between groups I and II, and groups II and III). The positive candidal culture rates were 12.5% (3/24) in group III, 11.5% (3/26) in group II, and 17.3% (9/52) in group I (p>0.05). CONCLUSIONS: Patients who received proton pump inhibitor had more acid suppression and intra-gastric bacterial infection than those of the control group. The intra-gastric candidal infection was not related to intra-gastric pH or anti-secretory medication in this study.     

Effects of very long (up to 10 years) proton pump blockade on human gastric mucosa

BACKGROUND: Long-term use of proton pump inhibitors (PPI) has been reported to worsen oxyntic mucosa gastritis and the resulting gland atrophy has been considered a potential risk factor for neoplastic changes in the gastric mucosa. AIMS: The present study examines the effect of extended continuous PPI treatment for up to 10 years on the exocrine and endocrine stomach of patients with acid-related diseases of the upper GI tract. METHODS: Biopsies from the antral and oxyntic mucosa taken at regular time intervals were examined for gastritis, atrophy, intestinal metaplasia, Helicobacter pylori and argyrophil cells and correlated to serum gastrin levels. RESULTS: A general amelioration of antral gastritis without relevant changes of atrophy or intestinal metaplasia, contrasted with the worsening of gastritis and gland atrophy seen in the oxyntic mucosa of reflux esophagitis (but not gastric or duodenal ulcer) patients in the presence of H. pylori infection. In association with PPI- induced hypergastrinemia, argyrophil cell hyperplasia (but not dysplasia or neoplasia) developed in the oxyntic mucosa. CONCLUSION: The present results outline the milder pretreatment pattern and higher proneness to PPI-related, H. pylori-restricted worsening of oxyntic mucosa gastritis in reflux esophagitis compared to gastric ulcer or duodenal ulcer patients. In addition, they confirm a substantial safety of long-term PPI therapy as concerns neoplastic changes in the exocrine and endocrine human stomach.     

Rabeprazole, 20 mg once daily or 10 mg twice daily, is equivalent to omeprazole, 20 mg once daily, in the healing of erosive gastrooesophageal reflux disease

BACKGROUND: Proton pump inhibitors are the most potent pharmacologic inhibitors of gastric acid secretion currently available, and have proven effective in the treatment of gastro-oesophageal reflux disease (GERD). The object of this study was to compare the efficacy and tolerability of a new proton pump inhibitor, rabeprazole at two different dosages, with that of omeprazole in the healing of erosive GERD. METHODS: Rabeprazole 20 mg once daily (QD) and 10 mg twice daily (BID) were compared with omeprazole 20 mg QD in a double-blind, multicentre, parallel group study involving 310 patients with erosive GERD. The primary efficacy endpoint was oesophageal mucosal healing determined by endoscopy. Secondary endpoints included reduction in symptoms and improvements in quality-of-life scores. RESULTS: The healing rates between both rabeprazole groups and the omeprazole group were equivalent in both the per-protocol and intent-to-treat populations. In the per-protocol population, rabeprazole 20 mg was noted to have a numerical trend toward more rapid daytime heartburn relief. However, by 4 and 8 weeks of treatment, no significant differences were found between groups for secondary endpoints, adverse events, or laboratory abnormalities including elevation of serum gastrin levels. CONCLUSIONS: Rabeprazole 20 mg in two different dosing schedules is as effective as omeprazole 20 mg QD with regard to efficacy and tolerability in patients with erosive GERD.     

Optimizing medical therapy for gastroesophageal reflux disease: state of the art

Potential interventions for gastroesophageal reflux disease include lifestyle modifications, antacids, mucosal protectants, prokinetic (promotility) agents, H2 receptor antagonists (H2RAs) and, the agents of choice in 2003, proton pump inhibitors (PPIs). This article reviews the current state of the art in use of these agents. Lifestyle changes, though sound in their intent and in many cases based on solid laboratory research, can today be considered only adjuncts to pharmacologic therapy. The mainstay of pharmacologic therapy in 2003 is antisecretory therapy. Both H2RAs and PPIs inhibit acid secretion and raise intragastric pH. H2RAs only block one receptor, have limited effect on acid reduction, and are relatively weak inhibitors of meal-stimulated acid secretion. PPIs provide superior control of intragastric pH over a 24-hour period compared with H2RAs and effect greater symptom relief and healing.     

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study

OBJECTIVES: Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. METHODS: This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. RESULTS: Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.     

Refractory heartburn to proton pump inhibitors: epidemiology, etiology and management

Patients with refractory heartburn to proton pump inhibitors (PPIs) represent a distinctive group which is difficult to manage. In a systematic review of the relative literature we found that approximately 20% of patients with erosive esophagitis and 15-25% of patients with normal endoscopy and abnormal 24-hour esophageal pH monitoring continue to report heartburn despite treatment with standard dose PPIs. Furthermore, approximately 30-40% of patients with normal endoscopy and 24-hour pH studies and 15-20% of patients with Barrett's esophagus have refractory heartburn to double dose PPIs. In such cases, compliance to therapy, duodeno-gastroesophageal reflux, gastro-esophageal motility disorders and eradication of Helicobacter pylori infection may contribute to symptoms. Based on the available evidence, we suggested an algorithm for the evaluation and management of these patients.     

Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer

Background and Aims:  After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer.
Methods:  Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72-h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72-h pH study.
Results:  Mean 72-h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion ( P  = 0.48). Mean 72-h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion ( P  = 0.62). Mean 72-h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. ( P  = 0.55). Mean 72-h pH for the no proton pump inhibitor group was 2.04.
Conclusion:  There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.     

根除幽门螺杆菌前后对痘疹样胃炎治疗效果的比较

目的:评价痘疹样胃炎根除幽门螺杆菌(H.pylori)后的治疗效果以及病理变化情况,明确根除H.pylori对痘疹样胃炎的治疗意义.方法:325例痘疹样胃炎患者根据H.pylori检测结果分为阳性组(标准三联或四联疗法)与阴性组(单纯抑酸),比较治疗效果;阳性组根据复查胃镜H.pylori的结果再分为两组,比较病理情况...     

Helicobacter pylori and luminal gastric pH

The relationships between gastric pH and Helicobacter pylori infection were studied in 37 consecutive subjects affected with nonulcer dyspepsia. Each underwent esophagogastroduodenoscopy with multiple gastric biopsies for both H. pylori and histologic assessment, and 24-hr antral pH monitoring. H. pylori was harbored by 59.5% of the subjects with whole gastric spread of infection in all but one patient. Histologic gastritis was shown in 70.3% of the subjects. H. pylori was strongly associated with gastritis, both antral nonatrophic and multifocal atrophic. The ranges of 24-hr pH values were 1.3-6.9 in the H. pylori-positive and 1.2-6.8 in the H. pylori-negative group. Differences in pH values between the two groups were not significant. Moreover, the mean percent time duration of pH above 2, 4, and 6 did not significantly differ between the two groups. Therefore, this study has shown that chronic H. pylori infection is not related to luminal gastric pH.     

Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough

BACKGROUND & AIMS: Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue. METHODS: Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. RESULTS: Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA. CONCLUSIONS: The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.     

Bile Reflux due to Disturbed Gastric Movement Is a Cause of Spontaneous Gastric Ulcer in W/Wv Mice

c-Kit is a receptor tyrosine kinase, and it isencoded by the mouse W locus. Mutant W/W^vmice develop spontaneous gastric antral ulcers. The aimof the present study was to investigate the pathogenesis of these gastric ulcers and to examine theeffects of two antiulcer drugs; a proton pump inhibitor(2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H-benzimidazole sodium salt, rabeprazole) and a mucosal protective drug(geranylgeranylacetone, GGA), on the gastric ulcers. Theinhibition of the gastric acid secretion by rabeprazole(30 mg/kg body weight, subcutaneous injection once a dayfor six weeks) significantly increased the gastriculcer formation compared to the controls. In contrast,the GGA treatment (100 mg/kg body weight, oraladministration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen inthese mutant mice, and they showed no cyclic intensecontractions in the gastric antrum. These resultssuggest that bile reflux due to the disturbance ofgastric antral movement is a cause of the spontaneousgastric ulcers in W/W^v mice.     

Current role of acid suppressants in Helicobacter pylori eradication therapy

Helicobacter pylori induces chronic active gastritis that may progress to atrophy. Serious clinical consequences are peptic ulcer disease and gastric malignancies. Today, treatment of the infection is an appropriate option and is strongly recommended in various clinical situations. Although many antibiotics are effective against H. pylori in vitro, few substances are suitable for use in vivo. This is because H. pylori lives in a unique environment in which several factors may affect the pharmacokinetic and pharmacodynamic properties of the anti-microbial agents. One of the most important factors is gastric acidity. This article reviews the effects of acid suppression on H. pylori and the associated gastritis, the potential mechanisms by which anti-secretory drugs such as proton pump inhibitors might enhance the activity of anti-microbials in vivo, and the results of clinical trials supporting the current view that proton pump inhibitors are a mainstay in the treatment of this infection.