Intragastric Acidity Research Articles

Nocturnal acid breakthrough: Clinical significance and management

AbstractNocturnal acid breakthrough is seen in more than 70% of Helicobacter pylori‐negative patients taking long‐term proton pump inhibitors (PPI). It is defined as an intragastric pH of less than 4 for at least 60 consecutive minutes during the overnight period in patients on PPI therapy. It occurs as a result of the recovery of intragastric acidity. Nocturnal acid breakthrough can be clinically significant in patients with complicated gastroesophageal reflux disease, Barrett’s esophagus and esophageal motility disorders because of the potential for continued esophageal mucosal injury. To decrease nocturnal acid breakthrough, for patients on once daily PPI, treatment should be stepped up to twice daily. For patients already on twice daily PPI, nocturnal histamine‐2 receptor antagonists may be added, but the long‐term effectiveness remains debatable as patients may develop tolerance over the course of time. New PPI with a longer half‐life may decrease nocturnal acid breakthrough.

A comparative study of intragastric acidity during post‐breakfast and pre‐dinner administration of low‐dose proton pump inhibitors: a randomized three‐way crossover study

The absorption and bioavailability of proton pump inhibitors is influenced by food intake. Proton pump inhibitors bind to the parietal cell active proton pump, which is maximally stimulated after dinner: usually the largest meal of the day. However, it has not been fully clarified whether the efficacy of proton pump inhibitors differs between post-breakfast and pre-dinner dosing. To perform a pH-monitoring study to clarify this issue for two low-dose proton pump inhibitors. The subjects were 20 healthy male volunteers (seven Helicobacter pylori-positive and 13 H. pylori-negative), who were divided into two groups of 10 and administered 15 mg lansoprazole or 10 mg rabeprazole, respectively. All subjects underwent ambulatory intragastric 24-h pH- monitoring under three conditions allocated randomly: (i) without medication, (ii) seventh day of post-breakfast administration and (iii) eighth day of pre-dinner administration of each drug. There was no significant difference in the percentage time during which pH > or =4.0 in the 24-h period between post-breakfast and pre-dinner administration of both drugs (56.6% vs. 55.8%; P = 0.557), although intragastric acidity during administration of both drugs was significantly lower than that without medication. The timing of drug administration does not significantly influence the efficacy of low-dose proton pump inhibitors.

Corpus‐predominant gastritis as a risk factor for false‐negative 13C‐urea breath test results

Urea breath test sensitivity seems affected by increased intragastric acidity during therapy with antisecretory drugs. Intragastric pH is increased in patients with corpus gastritis with/without atrophy. To test the hypothesis that urea breath test results may also be affected by this gastritis phenotype. 123 untreated patients underwent gastroscopy plus biopsies and intragastric pH measurement. The study included 82 endoscopically proven Helicobacter pylori-positive patients who were offered urea breath test with an acidic meal. Histological findings, urea breath test results and intragastric pH were compared in 66 of the subjects. 21 of 66 (31.8%) patients had a false-negative urea breath test. In these patients corpus-predominant gastritis (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001) were more frequent than in patients with true-positive urea breath test. Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P = 0.001). In a multivariate analysis, the only risk factor for a false-negative urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95% CI: 1.1-27). There was a negative correlation between the intragastric pH and the delta over baseline values (r = -0.378; P = 0.0023). Our results support the hypothesis that the pattern of gastritis can affect the sensitivity of urea breath test, and suggest that patients with corpus-predominant gastritis have a high risk of false-negative urea breath test results.

Safer endoscopic gastric mucosal resection: Preoperative proton pump inhibitor administration

Control of bleeding is crucial in improving the safety of endoscopic mucosal resection (EMR), and intragastric acidity has a great impact on hemostasis and blood coagulation. Proton pump inhibitors (PPI) are potent suppressors of gastric acid; however, PPI need to be continuously administered orally for several days, and thus initial effects may be insufficient if PPI is only administered immediately after EMR. The aim of this study was to determine whether preoperative administration of PPI prior to EMR can elevate intragastric acidity, facilitate better control of intraoperative bleeding (complete coagulation and hemostasis), prevent postoperative bleeding, and facilitate healing of artificial ulcers. A randomized clinical study was conducted in which EMR was performed with or without 1 week of preoperative PPI administration. Artificial ulcers created by EMR healed more rapidly in patients who received preoperative PPI. The results of the study suggest that preoperative administration of PPI before EMR is useful for controlling and preventing bleeding, and for facilitating the healing of artificial ulcers.

Effects of 3-day IV pantoprazole versus omeprazole on 24-hour intragastric acidity at 3 days in Chinese patients with duodenal ulcer: A single-center, prospective, randomized, comparative, pilot trial

Background: Pantoprazole and omeprazole are irreversible proton pump inhibitors that have been found to significantly reduce intragastric acidity in patients with peptic ulcer and/or esophagins. It has been reported that gastric acid secretion is lower in the Chinese patients compared with the Western population. Based on a MEDLINE search, no studies of the treatment of in tragastric acidity with IV pantoprazole have been conducted in the Chinese population to date. Objective: This trial was performed to compare the effects of IV pantoprazole versus omeprazole on 24-hour intragastric acidity in Chinese patients with endoscopically confirmed duodenal ulcer. Methods: This single-center, randomized, pilot study was conducted at the Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan. Chinese patients aged 18 to 80 years with endoscopically confirmed duodenal ulcer were randomly assigned to receive a continuous IV infusion of pantoprazole or omeprazole 160 mg/d for 3 days. On days 4 to 14, patients received pantoprazole 40 mg/d or omeprazole 20 mg/d orally. During endoscopic examination at enrollment, an antral biopsy specimen was obtained for rapid urease test, with each patient's agreement, by a blinded investigator. The primary end point was 24-hour intragastric pH on day 3. Secondary end points were percentage of the total time during the 24-hour period (%t) pH <3 and <4 and proportions of patients with healed ulcers on day-14 endoscopy. Endoscopic examination for monitoring of adverse effects of both drugs was repeated 8 weeks after study completion. Results: A total of 40 patients were enrolled (35 men, 5 women; mean age, 63.3 years; 20 per treatment group). Twenty-four-hour intragastric pH was not significantly different between the omeprazole and pantoprazole groups (mean [SD], 6.61 [1.27] vs 6.84 [0.78]). The %t pH <3 (mean [SD], 8.01% [19.60%] vs 2.70% [7.18%]) and pH <4 (mean [SD], 9.28% [21.41%] vs 3.87% [9.79%]) were not significantly different between the omeprazole and pantoprazole groups. On day-14 endoscopy, ulcers were found to be healed in 3 (15%) patients in each group. In the omeprazole group, 1 (5%) patient experienced mild diarrhea, and 1 (5%) experienced mild abdominal fullness. These adverse effects were considered treatment related. No adverse effects were reported in either treatment group at 8 weeks after the study. Conclusions: The results of this pilot study of 3-day treatment with a continuous IV infusion of pantoprazole or omeprazole 160 mg/d found that these 2 treatments had similar effects on 24-hour intragastric pH in this small population of Chinese patients with duodenal ulcer. Both treatments were well tolerated.

Comparative Efficacy of Rabeprazole and Pantoprazole in the Control of Nocturnal Gastric Acid Output and Intragastric Acidity—A Randomized, Two-Way Crossover Study

Purpose: Rabeprazole and other proton pump inhibitors (PPI) have been shown to be highly effective in the treatment of gastro-esophageal reflux disease (GERD). However, there has never been a rigorous investigation as to the comparative ability of PPIs when taken as per FDA label to control night-time GERD. In this study, we sought to evaluate the relative efficacies of rabeprazole and pantoprazole in controlling nocturnal gastric acid secretion. Methods: The study was conducted as a double-blinded, randomized crossover study enrolling 23 patients with a history of GERD without previous PPI treatment. The patients first underwent a baseline 12 hour overnight gastric analysis (2000 to 0800) whereby 30 minute samples were collected and assessed for acid output and intragastric pH. The subjects were randomized into 1 of 2 groups to receive either rabeprazole 20 mg or pantoprazole 40 mg on the morning of the next visit (Treatment 1). At that time, a second gastric analysis was completed in the above fashion. Following a 4 week washout, the subjects were given the other study drug (Treatment 2) and a third gastric analysis was completed. Acid output was determined using the titration method. Nocturnal acid breakthrough (NAB) was defined as persistence of gastric pH < 4 for greater than 1 hour between the hours of 22:00 and 06:00. Results: Rabeprazole achieved greater evening and nocturnal acid control compared with pantoprazole (median pH: 4.2 vs 3.9; mean time pH > 4: 5.5 vs 4.5 hours; NAB 50% vs 67%). A significantly greater percentage of patients on rabeprazole maintained an intragastric pH greater than 4.0 for more than 6 hours compared to pantoprazole (47% vs 27%). Rabeprazole achieved greater acid output control compared to pantoprazole (mean acid output:.78 vs 1.18 mEq/hr (p <.005); mean percentage of time acid output < 2: 92% vs 78%). Conclusions: Rabeprazole achieved significantly greater control of evening and night-time acid output, suggesting that it is a highly effective treatment for night-time GERD. In addition, a significantly greater percentage of patients on rabeprazole maintained an intragastric pH > 4 for more than half the study time with fewer incidences of NAB. These results demonstrate for the first time that control of nocturnal gastric acid secretion can be improved with rabeprazole compared to pantoprazole.

To Establish the Efficacy of PPI Therapy for Ulcer Bleeding in the United States, Do We Need More Patients or More PPIs?

Proton pump inhibitor (PPI) therapy is widely used in the management of patients with ulcer bleeding. However, most randomized controlled trials (RCTs) have been conducted outside of the United States. Jensen and colleagues have conducted the first United States-based RCT to compare a PPI with an H(2)-receptor antagonist following appropriate endoscopic hemostatic treatment for patients with ulcer bleeding. Unfortunately, the trial had to be discontinued prematurely because of problems with enrolment. There was a statistically nonsignificant difference in rebleeding rates between the two treatment arms. A type II statistical error probably explains this apparent lack of efficacy. However, U.S. patients may also require higher doses of PPI for adequate control of intragastric acidity.

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease

The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.

Gastric and Esophageal pH in Patients With Barrett's Esophagus Treated With Three Esomeprazole Dosages: A Randomized, Double-Blind, Crossover Trial

It has been suggested that patients with Barrett's esophagus (BE) are unusually resistant to the antisecretory effects of proton pump inhibitors (PPIs). To compare intragastric and intraesophageal acidity in patients with BE receiving esomeprazole 40 mg three times daily (t.i.d.), esomeprazole 40 mg twice daily (b.i.d.), and esomeprazole 20 mg t.i.d. In this randomized, double-blind, three-way crossover study, patients with long-segment BE received each of the three esomeprazole dosages for 5 days separated by 10-14-day washout periods. Intragastric and intraesophageal pHs were measured for 24 h on day 5. Among 31 patients with evaluable pH data, intragastric pH was >4.0 for 88.4%, 81.4%, and 80.4% of day 5 after treatment with esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. Esomeprazole 40 mg t.i.d. was significantly more effective than the other dosages (p < 0.01). Intraesophageal pH was <4.0 for mean values of <5% of the monitoring period with all the three dosing regimens, but esophageal pH remained <4.0 for >5% of the time in 16%, 23%, and 19% of patients receiving esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. All dosages were well tolerated. All the three esomeprazole dosages significantly decreased intragastric acidity and reduced esophageal acid exposure to mean normal values in the total group of patients with BE. However, abnormal esophageal acid exposure continued in 16-23% of patients despite the significant decrease in gastric acidity. These results suggest that the apparent "PPI resistance" described in patients with BE may be caused by their profound reflux diathesis rather than by gastric resistance to the antisecretory effects of PPIs.

Tenatoprazole timing doesn't alter intragastric acidity inhibition

Tenatoprazole timing doesn't alter intragastric acidity inhibition

Review article: the opportunities and benefits of extended acid suppression

Acid suppression therapy with proton pump inhibitors is associated with well-established benefits in the management of gastro-oesophageal reflux (GERD) and other acid-related disorders. However, a number of issues still remain unsettled. Despite their clinical efficacy, when given once daily, currently available proton pump inhibitors may not adequately control intragastric acidity during the night in a significant proportion of both healthy subjects and GERD patients, in whom symptom relief remains suboptimal. Although some novel proton pump inhibitors have been synthesized, only few reached clinical testing. Amongst them, tenatoprazole represents a true advance displaying a long half-life (five to seven times longer than that of currently available drugs) and extended acid suppression covering both day and night. All the available clinical studies suggest both pharmacokinetic and pharmacodynamic advantages of tenatoprazole over esomeprazole. As this last compound provides - amongst the members of the class - the most effective control of intragastric pH whatever the parameter considered, it is conceivable that tenatoprazole could similarly be better than the other existing proton pump inhibitors. Tenatoprazole appears to be a promising proton pump inhibitor for the treatment of acid-related diseases, where it has the potential to address unmet clinical needs.

Intragastric acidity after switching from 5-day treatment with intravenous pantoprazole 40 mg/d to 5-day treatment with oral esomeprazole 40 mg/d or pantoprazole 40 mg/d: An open-label crossover study in healthy adult volunteers

Background: After a course of IV proton pump inhibitor therapy, patients might require continued oral antisecretory therapy. A direct comparison of therapeutic alternatives could assist physicians in decisions regarding optimal acid-suppressive therapy. Oral esomeprazole might control intragastric acidity more effectively compared with other acid-suppressive agents after IV therapy. Objective: The aim of this study was to compare intragastric acid control on day 5 of administration of esomeprazole magnesium versus pantoprazole 40 mg PO QD after switching from 5 days of treatment with pantoprazole 40 mg IV in healthy volunteers. Methods: This randomized, open-label, comparative, 2-way crossover study was conducted at the Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, between October and December 2004. Healthy, Helicobacter pylori-negative adults were randomly assigned to 1 of 2 dosing sequences: pantoprazole IV followed by esomeprazole PO or pantoprazole IV followed by pantoprazole PO. All study medications were administered for 5 days at a dose of 40 mg QD. IV pantoprazole was administered over 2 minutes; all medications were administered 30 minutes before breakfast. There was a 10- to 21-day washout period between each 10-day dosing period. All doses were administered at the study site. Before oral study drug administration on days 1 and 5, 24-hour pH monitoring was performed using a pH catheter positioned 10 cm distal to the lower esophageal sphincter in the stomach. The primary end point was percentage of time with pH >4 (%t pH >4) during the 24-hour pH-monitoring period. Tolerability was assessed using spontaneous reporting, laboratory analysis, and vital-sign measurement. Results: Of 42 subjects randomized to treatment sequences, 4 were withdrawn during the study because of invalid pH data; 38 subjects (24 men, 14 women; mean [SD] age, 25.2 [8.1] years) had assessable data. Day-5 %t pH >4 was 68.5% with esomeprazole and 53.3% with pantoprazole ( P < 0.001). Day-1 %t pH >4 was 62.5% with esomeprazole and 51.0% with pantoprazole ( P < 0.001). The most common adverse events were rhinitis (2 subjects each with pantoprazole IV and PO; 1 subject with esomeprazole) and headache (2 subjects with esomeprazole; 1 subject with pantoprazole IV). Conclusions: The results of this study in healthy adult volunteers suggest that switching from pantoprazole 40 mg IV to esomeprazole 40 mg PO QD more effectively suppresses intragastric acid compared with switching from pantoprazole 40 mg IV to pantoprazole 40 mg PO QD. All 3 treatments were well tolerated.

Intragastric acid control in non‐steroidal anti‐inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole

Studies to date have not directly compared the pharmacodynamic efficacies of different proton pump inhibitors in controlling intragastric acidity in patients treated with non-steroidal anti-inflammatory drugs. To compare acid suppression with once-daily esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drug therapy. In this multicentre, open-label, comparative, three-way crossover study, adult patients (n = 90) receiving non-steroidal anti-inflammatory drugs were randomized to one of six treatment sequences. At the study site, patients were administered esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg for 5 days each, with a washout period of > or =10 days between each treatment. Twenty-four-hour pH testing was performed on day 5 of each dosing period. The mean percentage of time during the 24-h pH monitoring period that gastric pH was >4.0 was significantly greater with esomeprazole (74.2%) compared with lansoprazole (66.5%; P < 0.001) and pantoprazole (60.8%; P < 0.001), and significantly greater with esomeprazole (P < 0.05) than with the comparators regardless of whether using non-selective vs. cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs. At the doses studied, esomeprazole treatment provides significantly greater gastric acid suppression than lansoprazole or pantoprazole in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs.

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 study

The effectiveness of proton pump inhibitors is influenced by meals and administration time. 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. 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. 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). 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.

Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans

To observe the pharmacokinetics and pharmaco-dynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.

Analysis of the acidity index and integrated intragastric acidity in 645 patients presenting with gastroesophageal reflux disease symptoms

Objective. In a recent study of patients receiving proton-pump inhibitor (PPI) therapy, a new parameter, the acidity index, was described as being less complicated to calculate and of comparable accuracy (r=0.93) to integrated intragastric acidity (IA) in assessing intragastric pH control. The aim of this study was to correlate AI with IA using a large database of ambulatory 24-h pH-metry studies in untreated patients presenting with gastroesophageal reflux disease (GERD) symptoms. Material and methods. We retrospectively analyzed 645 studies obtained from 1995 to 2001. Daytime (0800 h–2200 h), night-time (2200 h–0800 h) and 24-h IA and AI were calculated according to age, gender and the presence or absence of GERD, and correlations between these parameters were assessed using linear regression with F-statistic values, p-values and Akaike's Information Criterion values. GERD was defined as total esophageal pH time <4.0, 5 cm above the lower esophageal sphincter, for ≥4.2% of the day. IA and AI were calculated as follows: IA (mmol.h/l) = ∑(acid in mmol/l at time “t” + acid in mmol/l at time “t − 1”)/2×(“t”–“t − 1”); AI=(%time pH < 4–%time pH < 3)×1+(%time pH < 3–%time pH < 2)×10+(%time pH < 2–%time pH < 1)×100+(%time pH < 1–%time pH < 0.8)×1000. Results. Overall, the mean 24-h IA value was 882.0±820.0 mmol.h/l (daytime 392.0±400.0, night-time 490.0±486.0). The mean 24-h AI value was 102.0±87.0 (daytime 86.0±80.0, night-time 120.0±114.0, p<0.001). The mean 24-h IA value was 1057.0±829.4 mmol.h/l (daytime 459.8±406.0, night-time 597.2±500.4, p<0.001) in GERD patients and 713.0±775.0 mmol.h/l (daytime 326.0±383.0, night-time 387.0±448.5) in non-GERD patients (p<0.001). The mean 24-h AI value was 122.1±88.1 (daytime 101.4±82.5, night-time 145.3±120.7) in GERD patients and 83.0±81.0 (daytime 71.0±73.9, night-time 96.4±102.6) in non-GERD patients (p<0.001). Our statistical modeling demonstrated that the correlation between the acidity index and IA becomes progressively poorer with increasing values of acidity. Conclusions. We conclude that gastric acid production assessed by both IA and AI is higher during evening hours in comparison with daytime hours and the difference between night-time and daytime values is statistically significant. In addition, gastric acid production assessed by both IA and AI is significantly higher in GERD patients than non-GERD patients. This difference is primarily due to differences in nocturnal acid production. The AI correlates poorly with measured IA, especially at higher levels of gastric acidity. Therefore, AI is not an acceptable surrogate for IA in assessing gastric acid production.

The effect of regular and high doses of omeprazole on the intragastric acidity in patients with bleeding peptic ulcer treated endoscopically: a clinical trial with continuous intragastric pH monitoring

In peptic ulcer bleeding (PUB), pH level >4 is considered necessary to prevent dissolving of a formed fibrin clot. The effect of regular or high doses of omeprazole on the intragastric pH in patients with acute PUB was studied. In our earlier study, after endoscopic therapy, PUB patients were randomized to receive a regular dose of intravenous omeprazole (20 mg; i.e. 60 mg/3 days) or a high dose of omeprazole (80 mg bolus + 8 mg/h; i.e. 652 mg/3 days). Of these 142 analysed and reported patients, 13 PUB patients also had intragastric pH monitoring for these 3 days; seven of these patients had a regular dose and six received a high dose of omeprazole. The mean 24-h intragastric pH (regular versus high dose) on day 1 was 4.9 +/- 1.6 versus 6.3 +/- 0.5 (P = 0.035), on day 2 was 4.9 +/- 1.8 versus 6.7 +/- 0.3 (P = 0.001), and on day 3 was 5.7 +/- 1.1 versus 6.7 +/- 0.5 (P = NS). The medians of the intragastric pH were 6 versus 6.5 (P = 0.082) on day 1, 5.8 versus 6.8 (P = 0.001) on day 2, and 6.2 versus 6.8 (P = 0.17) on day 3. The proportion of time when pH <4 on day 1 was 29.2 +/- 34.1 versus 5.4 +/- 5.7% (P = NS). A regular dose of omeprazole raises the mean and median 24-h intragastric pH >4 in patients with PUB. This reduction in the acidity together with endoscopic therapy is probably sufficient to maintain haemostasis. A high dose of omeprazole keeps the pH almost constantly >6.

Impact of Helicobacter pylori eradication on the anti‐secretory efficacy of lansoprazole in gastroesophageal reflux disease patients

Helicobacter pylori eradication was recommended for the prevention of atrophic gastritis in gastroesophageal reflux disease (GERD) patients on long-term omeprazole treatment. It has been also shown that the treatment with proton pump inhibitors produces lower intragastric pH after H. pylori eradication in subjects with peptic ulcer and healthy individuals. The aim of the present study was to test the hypothesis of whether the efficacy of lansoprazole is reduced after the eradication of H. pylori in GERD patients with peptic esophagitis. Eight-hour intragastric pH recordings were performed before and after an 8-day course of lansoprazole (30 mg once daily) in 10 H. pylori-positive male patients with reflux esophagitis and were repeated after the H. pylori eradication. Intragastric acidity was measured by using an antimony electrode placed 10 cm below the cardia. Baseline median preprandial, post-prandial, total intragastric pH and the percentage of time with pH < 3 were not different before and after H. pylori eradication without lansoprazole treatment. During lansoprazole treatment, median post-prandial intragastric pH was lower (4 vs 2.7; P < 0.05) and the percentage of time with pH < 3 was longer (3.4%vs 41.8%; P < 0.05) after H. pylori eradication. Median total intragastric pH tended to be lower after eradication but no difference was found in preprandial median pH. In patients with reflux esophagitis treated with lansoprazole, intragastric pH increased significantly when H. pylori was present, especially in the post-prandial period, whereas baseline pH remained unchanged after H. pylori eradication.

Effect on Intragastric pH of a PPI with a Prolonged Plasma Half-Life: Comparison between Tenatoprazole and Esomeprazole on the Duration of Acid Suppression in Healthy Male Volunteers

To compare the inhibitory effect of a novel proton pump inhibitor (PPI), tenatoprazole 40 mg once daily, with esomeprazole 40 mg once daily on intragastric acidity. A randomized, investigator-blind, two-way, crossover study was conducted in 30 healthy Helicobacter pylori negative male volunteers. Tenatoprazole 40 mg or esomeprazole 40 mg was administered once daily for 7 consecutive days with a 4-wk washout period between treatments. Ambulatory 24-h intragastric pH was recorded at baseline, after 7 days' treatment, and 3 and 5 days after treatment was stopped. At presumed steady-state (day 7), median 24-h pH values were 5.02 and 4.79 for tenatoprazole and esomeprazole, respectively. There was a significant difference between tenatoprazole and esomeprazole during the nocturnal period when mean pH was 4.64 +/- 0.67 versus 3.61 +/- 0.90, respectively (p < 0.0001), as well as a significantly higher mean percentage of time with pH >4 on tenatoprazole (72.5 +/- 14.9 vs 62.2 +/- 13.6, p < 0.0001). The effect of tenatoprazole was still present 5 days after treatment withdrawal especially during the night-time. The mean area under the plasma concentration-time curve and elimination half-time was significantly higher in the tenatoprazole group as compared with the esomeprazole group. Tenatoprazole 40 mg daily provides a prolonged duration of acid suppression and a shorter nocturnal acid breakthrough in healthy volunteers, even after stopping the drug. Thus, tenatoprazole may provide greater clinical efficacy for patients in whom a once daily PPI is ineffective. Further studies are indicated.

Effect of Single Doses of Rabeprazole 20 mg and Pantoprazole 40 mg on 24-Hour Intragastric Acidity in Gastroesophageal Reflux Disease (GERD) Patients with Nocturnal Heartburn

Purpose: PPIs with rapid and prolonged control of acid secretion may be useful for treating nocturnal GERD symptoms. This study compared the antisecretory effects of single doses of rabeprazole sodium (RAB) 20 mg and pantoprazole sodium (PAN) 40 mg tablets in patients with a clinical diagnosis of GERD and a history of nocturnal heartburn (≥1 episode/wk). Methods: This open-label, randomized, 2-way crossover comparison enrolled H pylori-negative subjects to receive RAB 20 mg and PAN 40 mg (single oral doses) in the morning (≥14-day washout). Intragastric pH was measured from 24 h before (day 0) until 24 h after dosing (day 1). Patients fasted from 2200 h the evening before until ∼0900 h on day 0 and 1, and had standard meals/drinks 1, 4, and 10 h after dosing on day 1 and at corresponding times on day 0. Primary end point was 24-h area under intragastric pH–time curve (AUC0–24) on days 0 and 1. Secondary end points included AUC for 0–5, 5–11, 11–14, and 14–24 h;% time pH >3 and >4 over 24 h and for 0–14 and 14–24 h; and safety/tolerability. Results: 31 patients (male, n = 19; mean age, 44 yr) were enrolled (evaluable population, n = 29). Preliminary results show that day-1 mean intragastric pH AUC0–24 was significantly higher for RAB vs PAN: 319,692 vs 259,921 pH units. sec, respectively (evaluable population; P < 0.0001). In the ITT and evaluable (Table 1) populations, mean pH AUC was significantly higher for RAB (P ≤ 0.024) in all time intervals studied, including overnight (14–24-h). Mean day 1% time pH >3 and >4 was significantly higher for RAB (P ≤ 0.004) during the 24 h after dosing and all time intervals (ITT and evaluable populations). Both treatments were well tolerated.Table: No Caption available.Conclusions: Overall and during all time intervals, including overnight, a single oral dose of RAB 20 mg increased intragastric pH more than did PAN 40 mg in GERD patients with nocturnal heartburn. Research supported by Eisai Ltd., London, UK; Eisai Inc., Teaneck, NJ, USA; and Janssen Pharmaceutica Inc., Titusville, NJ, USA.