Intragastric pH Measurement Research Articles

A translational pharmacokinetic/pharmacodynamic approach supports optimal vonoprazan dosing for erosive oesophagitis and Helicobacter pylori infection.

Treatment of acid-related disorders relies on gastric acid suppression. The percentage of time intragastric pH is >4 (pH >4 holding time ratio [HTR]) is important for healing erosive oesophagitis; and the pH >6 HTR is critical for eradication of Helicobacter pylori infection, as bacterial replication is active and antibiotic effectiveness is optimised. Vonoprazan, a potassium-competitive acid blocker approved in the USA and other countries, suppresses gastric acid secretion in a predictable, rapid and consistent manner, extended over prolonged periods. To explore the relationship between vonoprazan exposure and pH HTR through a pharmacokinetic/pharmacodynamic (PK/PD) model. We pooled data from Phase 1 studies with intragastric pH measurements. Pharmacokinetic profiles were predicted for study participants using an existing population pharmacokinetic model. Pharmacokinetic and pharmacodynamic data were merged, and three direct-link PK/PD models were derived and used to simulate pH HTRs with between-participant variability for pH >4, >5 and >6, for vonoprazan doses of 20 mg once and twice daily. We used data from five Phase 1 studies to derive the PK/PD model. These included 245 participants (95.1% male, 50.6% Japanese and 49.4% non-Asian). Pre-dose, the mean pH >4 HTR was 6.4%, pH >5 3.2% and pH >6 1.2%. After 7 days of dosing, simulations predicted pH >4 HTRs of 89.7% and 98.1%, and pH >6 HTRs of 53.1% and 75.3%, for vonoprazan 20 mg once and twice daily, respectively. Vonoprazan 20 mg once- and twice-daily dosing demonstrated high, dose-dependent, 24-hour intragastric acid control in this PK/PD model, supporting clinical efficacy data in patients with acid-related disorders.

Pharmacodynamics and pharmacokinetics of DWP14012 (fexuprazan) in healthy subjects with different ethnicities.

DWP14012 (fexuprazan), a novel potassium-competitive acid blocker, is under development for the treatment of acid-related disorders. To compare the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of DWP14012 among healthy subjects of Korean, Caucasian and Japanese descent. A randomised, double-blind, placebo-controlled, single- and multiple-dose study was conducted. Ten subjects in each dose group (40, 60 or 80mg for Koreans; 40 or 80mg for Caucasians; 20, 40 or 80mg for Japanese) were randomly assigned to DWP14012 or a placebo. Twenty-four-hour intragastric pH measurements and serial blood samples were collected for PK/PD evaluation. The PK/PD parameters were compared between each ethnicity. The extent of gastric acid suppression was similar among the ethnicities; the mean percentages of time that the intragastric pH was above 4 after multiple doses of 40mg in the Korean, Caucasian and Japanese subjects were 64.3%, 62.8% and 70.3%, respectively, and the corresponding values for the 80mg dose were 94.8%, 90.6% and 90.6% respectively. The changes in serum gastrin were not clinically significant between all three ethnicities. The systemic exposure of DWP14012 was similar between the three ethnicities after the 40mg doses but slightly lower in Caucasian and Japanese subjects after the 80mg doses. Gastric acid suppression by DWP14012 showed a clear exposure-response relationship in the three ethnicities. Gastric acid suppression by DWP14012 was similar among the Korean, Caucasian and Japanese subjects in this study, and the PK, PK-PD relationships and safety were also similar among the three ethnicities. DWP14012 could be used without consideration of ethnicity.

Intragastric pH effect of 20 mg of levo-pantoprazole versus 40 mg of racemic pantoprazole the first seven days of treatment in patients with gastroesophageal reflux disease

Introduction/aimLevo-pantoprazole, the S-enantiomer of pantoprazole, is a proton pump inhibitor that has been shown in animal studies to be faster and stronger than its racemic formulation. There are no studies on humans and therefore our aim was to evaluate the effects of levo-pantoprazole versus racemic pantoprazole on intragastric pH. Materials and methodsA randomized controlled study was conducted on patients with erosive gastroesophageal reflux disease that were given 20mg of levo-pantoprazole (n = 15) versus 40mg of racemic pantoprazole (n = 15) for 7 days. Baseline and end-of-treatment symptom evaluation and intragastric pH measurement were carried out. ResultsThere were no differences between the groups in the baseline evaluations. From 40 to 115min after the first dose of levo-pantoprazole, the mean intragastric pH was higher, compared with that of racemic pantoprazole (p < 0.05). After one week, levo-pantoprazole and racemic pantoprazole significantly reduced intragastric acid production and its esophageal exposure (p < 0.05). Even though there was no statistically significant difference, a larger number of patients that received levo-pantoprazole stated that their heartburn improved within the first 3 days. ConclusionsThe S-enantiomer of pantoprazole (levo-pantoprazole) had a faster and stronger effect with respect to acid suppression, compared with its racemic formulation. Although the effect on symptoms was faster with levo-pantoprazole, occurring within the first days of treatment, it was equivalent to that of the racemate at one week of treatment.

Pharmacokinetics and pharmacodynamics of an orally disintegrating tablet formulation of dexlansoprazole.

Background:The pharmacokinetics and pharmacodynamics of a novel orally disintegrating tablet (ODT) formulation of delayed-release dexlansoprazole 30 mg was evaluated versus the dexlansoprazole 30 mg capsule in this phase I, open-label, multiple-dose, randomized, two-period crossover study.Methods:Healthy adults received daily doses of 30 mg dexlansoprazole ODT or 30 mg dexlansoprazole delayed-release capsule for 5 days during two treatment periods, separated by a 7-day washout interval. Blood samples for dexlansoprazole plasma concentrations and intragastric pH measurements were collected through 24 hours postdose on days 1 and 5 of each period.Results:Bioequivalence between the 30 mg ODT and 30 mg capsule dosage forms was demonstrated by the primary endpoints of dexlansoprazole peak concentration (Cmax) and systemic exposure (AUC) values contained within the prespecified 90% confidence interval (CI) range of 0.80–1.25. Additional primary endpoints of intragastric mean pH values and percentage of time with pH > 4 over the 24-hour postdose interval were equivalent for dexlansoprazole ODT and dexlansoprazole capsule. Treatment-emergent adverse events were reported in 23% and 28% of participants receiving the ODT and capsule formulations, respectively. Headache was the most common adverse event in both treatment regimens (5.8% with ODT and 6.0% with capsule).Conclusions:Administration of dexlansoprazole 30 mg ODT or 30 mg capsule provided equivalent plasma exposure when either was administered as a single dose or as once daily doses for 5 days. Pharmacodynamic equivalence between the two formulations was demonstrated by similar intragastric pH parameters on both day 1 and day 5. No effect of day on dexlansoprazole pharmacokinetics was observed. Dexlansoprazole ODT and dexlansoprazole capsule were both well tolerated.

High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea.

Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance.

Preprocedural Rabeprazole Treatment Before Endoscopic Submucosal Dissection for Gastric Neoplasms

The maximal effect of proton pump inhibitors (PPI) is reported to take 5 days. However, most current protocols start PPI on the day of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the benefit of 5 days pretreatment with oral PPI before ESD to prevent bleeding. This was a prospective randomized controlled trial. Patients were administered oral rabeprazole 20 mg or placebo twice daily for 5 days before ESD. Intravenous pantoprazole 40 mg was administered 2 h before ESD and at postprocedure day 1, and then oral rabeprazole 20 mg was administered once daily. Follow-up endoscopy was performed on days 1 and 30. Forty-eight-hour measurement of intragastric pH was performed in 26 patients. The primary endpoint was major bleeding related to ESD. One-hundred and twenty patients were enrolled. Of these, 45 in the pretreatment and 53 in the placebo group were analyzed. Each group had three cases of major bleeding. There were no significant differences in the ulcer healing rate. Intragastric pH percentage times greater than 4, 5, and 6 were 86.61 ± 19.45 %, 83.30 ± 22.06 %, and 76.86 ± 25.35 %, respectively, in the pretreatment and 85.54 ± 19.45 %, 84.08 ± 27.11 %, and 81.53 ± 27.81 %, respectively, in the placebo group, without significant differences. Preprocedural administration of rabeprazole offers no additional benefit over postprocedural administration alone in preventing major bleeding after gastric ESD.

Dose-dependent food allergy induction against ovalbumin under acid-suppression: A murine food allergy model

Background Animal models are essential for analyzing the allergenic potential of food proteins and for investigating mechanisms underlying food allergy. Based on previous studies revealing acid-suppression medication as risk factor for food allergy induction, we aimed to establish a mouse model mimicking the natural route of sensitization in patients. Methods The effect of acid-suppressing medication on murine gastric pH was assessed by intragastric pH measurements after two injections of a proton pump inhibitor (PPI). To investigate dose-dependency, mice were fed different concentrations of ovalbumin (OVA; 0.2, 0.5, 1.0, 2.5 or 5.0 mg) either with or without anti-ulcer medication. Additionally, different routes of exposure (i.p. vs. oral) were compared in a second immunization experiment. Sera were screened for OVA-specific antibody titers (IgG1, IgG2a and IgE) in ELISA and RBL assay. Clinical reactivity was evaluated by measuring rectal temperature after oral challenge and by type I skin tests. Results Two intravenous injections of PPI significantly elevated the gastric pH from 2.97 to 5.3. Only oral immunization with 0.2 mg OVA under anti-acid medication rendered elevated IgG1, IgG2a and IgE titers compared to all other concentrations. Protein feeding alone altered antibody titers only marginally. Even though also i.p. immunizations induced high levels of specific IgE, only oral immunizations under anti-acids induced anaphylactic reactions evidenced by a significant decrease of body temperature. Conclusion Only low-dosage ovalbumin feedings under anti-acid medication resulted in IgE mediated food allergy. Based on this knowledge we have established a suitable food allergy model for further investigations of food adverse reactions.

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 trial

Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. 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. 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. 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. 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.

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.

EFFICACY OF GASTRIC ACID‐LOWERING THERAPY IN THE DOG

Introduction: Gastric acid suppression is a recommended therapy for gastric ulceration. Human studies suggest that optimal healing of duodenal ulcers occurs at gastric pH &gt;3 for 75% of the day. The objective of this study was to evaluate the efficacy of 4 gastric acid suppressants at recommended veterinary doses. Drug effect was based on the 24‐hour median pH and the percentage of time that the intragastric pH ≥3 in a 24 hour period.Methods: The study was conducted in 12 healthy Beagle dogs and was a double‐blind, randomized, multiple cross‐over comparison of a placebo (saline IV q12 h), ranitidine 2 mg/kg IV q12 h, famotidine 0.5 mg/kg IV q12 h, pantoprazole 1 mg/kg IV q24 h, and omeprazole (unblinded) ∼1 mg/kg PO q24 h. Continuous 24‐hour intragastric pH measurements were obtained via PEG tube. Prior to drug testing, 24‐hour pH measurements were recorded in fasted and fed dogs. Thereafter, dogs were fed standardized meals throughout the remainder of the study period. Drugs were administered for 1 week with a one‐week washout period between tests. Data were obtained on Day 0 (baseline), Day 2 and Day 6 of treatment. Following the randomized study, famotidine 0.5 mg/kg IV q8 h and omeprazole ∼1 mg/kg + bicarbonate q12 h via PEG tube were evaluated in 6 dogs, respectively. Appropriate statistical analyses were applied to calculate the 24‐hour median pH and percentage of time that the test drug maintained intragastric pH≥3 over 24 hours.Results: The 24‐hour median pH of fasted dogs was 4.44 vs. fed dogs 1.30 (p&lt;0.0001). The % time pH≥3: fasted dogs 66.0% vs. fed dogs 13.3% (p&lt;0.0001). The 24‐hour median pH was (bold denotes significance when compared to saline) ‐ saline pH 1.81, ranitidine Day 2–pH 2.53, Day 6–pH 2.05, famotidine Day 2–pH 2.83, Day 6–pH 3.68, pantoprazole Day 2–pH 3.11, Day 6–pH 3.49, omeprazole Day 2–pH 3.86, Day 6–pH 4.09. The % time pH≥3: saline 32.9%; ranitidine day 2 – 44.6%, Day 6 – 37.2%; famotidine: Day 2 – 48.9%, Day 6 – 60.1%; pantoprazole: Day 2 – 54.2%, Day 6 – 59.1%; omeprazole: Day 2 – 66.9%, Day 6 – 70.2%. The 24‐hour median pH of omeprazole + bicarbonate q12 h was 4.7 on Day 2 and 4.9 on Day 6; the % time pH ≥3 was 90.9% on Day 2 and 78.4% on Day 6, respectively. No significant difference was noted in any parameter comparing famotidine q8 h and q12 h.Conclusions: Fasted dogs had a significantly higher pH than fed dogs. Omeprazole was the only drug tested that approached the potential therapeutic efficacy for healing of duodenal ulcers when assessed by criteria for human patients. Variation existed amongst dogs in all drugs tested.

Impaired gastric secretion and lack of trophic responses to hypergastrinemia in M 3 muscarinic receptor knockout mice

Background & Aims : The physiologic significance of the M 3 muscarinic receptor is unclear due to an absence of specific ligand. In the present study, M 3 receptor knockout (KO) mice were used to elucidate the role of M 3 receptors in gastric acid secretion and gastric mucosal integrity. Methods : M 3 KO versus wild-type mice aged 1 month to 2 years were included. Gastric acid secretion was assessed by both direct intragastric pH measurement and pylorus ligation. Serum gastrin and gastric mucosal histamine levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Morphologic analysis was performed by both immunohistochemistry and transmission electron microscopy. Results : Fasted M 3 KO mice exhibited higher intragastric pH, lower acid output after pylorus ligation, a lower proportion of active parietal cells, and higher serum gastrin levels than fasted wild-type mice. Acid secretion in response to carbachol, histamine, gastrin 17, and 2-deoxy- d-glucose was impaired in the mutant mice. Although carbachol was still able to cause ∼30% acid output in M 3 KO mice, the acid secretion was inhibited by pirenzepine or famotidine. Despite remarkable hypergastrinemia in M 3 KO mice, there were no trophic responses in the oxyntic mucosa with respect to the mucosal thickness, proliferation rate, and numbers of parietal and enterochromaffin-like cells. Cholecystokinin type 2 receptor antagonist YM022 was without the effect in M 3 KO mice. Conclusions : The present study shows that M 3 receptors are essential for basal acid secretion, a fully acid secretory response to histamine and gastrin, and the trophic responses of oxyntic mucosa to gastrin.

Multipoint measurement of intragastric pH in healthy preterm infants

Background: The diagnostic use of 24 hour oesophageal pH monitoring in infants is controversial because of the impact of feed buffering of gastric acidity. Aim: To re-evaluate the effect of...

The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

24-h Recording of Intragastric pH: Technical Aspects and Clinical Relevance

Background : Information about gastric acid secretion and gastric acidity can be obtained using several techniques but, presently, continuous intragastric pH recording is probably the one applied most frequently. This paper aims to review the technical aspects and some important applications of intragastric pH monitoring in research and clinical practice. Methods : Literature review. Results : Most studies on intragastric pH are performed with either glass or antimony electrodes. Optimal measurement of 24-h intragastric pH requires accurate calibration of the pH measuring system, exact positioning of the pH electrodes, and a sufficient sample rate. Depending on the aim of the study the results of intragastric pH monitoring are expressed either as median H + activity or as median pH values. Gastric acidity shows a circadian rhythm, modified by buffering meals and nocturnal duodenogastric reflux. In health, age, gender and smoking habits are known to influence gastric acidity. In duodenal ulcer disease an increased gastric acidity is found and in patients with gastric ulcer gastric acidity is decreased. In GERD, no relation between reflux oesophagitis and gastric acidity is found. Helicobacter pylori affects intragastric pH most pronounced during acid inhibitory therapy, both in DU patients and in healthy subjects. In the absence of H. pylori the effect of proton-pump inhibitors on intragastric pH is much less than in the presence of the microorganism, whereas the effect of ranitidine on intragastric pH is barely affected by the H. pylori status. Conclusions : Despite some limitations, intragastric pH monitoring provides important information about gastric acidity.

Effect of enprostil on omeprazole-induced hypergastrinemia and inhibition of gastric acid secretion in peptic ulcer patients.

This study was performed to examine the effects of additional enprostil administration on hypergastrinemia and gastric acid suppression induced by omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative patients) before treatment, after two weeks of omeprazole (20 mg/day), and after two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid inhibitory effect of enprostil was evaluated by 24-hr intragastric pH measurements in five healthy Helicobacter pylori-negative volunteers. After omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive patients (3.5-fold of control) was markedly higher than that of Helicobacter pylori-negative patients (1.7-fold of control). Additional treatment with enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recorded during the nonmeal daytime interval increased significantly with additional enprostil. Thus, enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positive patients, and effectively suppresses acid secretion.

48-Hour Continuous Intragastric pH Fluctuation During Lansoprazole Administration Every Other Day

The inhibitory effect on acid secretion of lansoprazole administered every other day in comparison with cimetidine was investigated in this study. Drugs and dosages were assigned to patients with peptic ulcer as follows: cimetidine 800 and 400mg daily; lansoprazole 30mg every other day. The patients’ intragastric pH was continuously measured, and the time at or above pH 4 (pH 4 holding time) was assessed. Total measurement time and night-time pH 4 holding times were 48.4 ± 3.7% and 56.1 ± 5.7%, respectively, with cimetidine 800mg; 33.7 ± 4.9% and 51.1 ± 7.3%, respectively, with cimetidine 400mg; and 66.1 ±6.1 % and 67.9 ± 5.6%, respectively, with lansoprazole every other day, revealing a significantly more powerful acid suppression in the lansoprazole than in the cimetidine groups. In addition, according to continuous 48-hour intragastric pH measurements, the pH 4 holding time during lansoprazole treatment days was significantly longer than on nontreatment days. Changes in patients’ blood gastrin levels over 48 hours while taking lansoprazole every other day revealed slightly higher values, depending on the time period, but 86% of the patients had fasting gastrin levels of 160 ng/L or less. When lansoprazole was administered every other day, the pH 4 holding time differed between the two days, and gastrin elevation was smaller. We suggest that lansoprazole every other day seems to be pharmacologically capable of being used just for peptic ulcer maintenance therapy.

Etiology of gastric remnant cancer with special reference to the effects of denervation of the gastric mucosa.

Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. Using male Wistar rats, four groups of Billroth I (B-I)gastrectomy, Billroth II (B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff--Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS-AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer.

Optimizing acid suppression for treatment of acid-related diseases

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Problems with the interpretation of gastric pH measurement.

The present study examines some of the assumptions underlying the use of intragastric pH-metry for assessing the degree of therapeutic gastric inhibition. Three separate studies were performed to determine the relationship between pH and titratable hydrogen ion concentration in gastric juice and to assess the relationship between the concentration of acid and the rate of gastric secretion. The concentration of acid derived from pH measurements tended to be lower than the titrated hydrogen ion concentration. The difference between the two readings--the "buffered" hydrogen ion concentration--was increased by the presence of food and was reduced during gastric secretory inhibition with ranitidine. The titrated hydrogen ion concentration reflected more accurately the amount of hydrochloric acid added to a container in vitro than pH measurement. However, in vivo even the measurement of titratable acidity was poorly correlated with the volume of secreted gastric juice so that measurement of gastric acid concentration does not permit inferences about the rate of gastric secretion. The results of the present study indicate that measurement of intragastric pH is unsatisfactory for assessing gastric secretion, particularly in response to a food stimulus, so that measurement of gastric acidity alone does not reflect the rate, or changes in the rate, of gastric acid secretion.

The Effect of Continuous Enteral Nutrition on Gastric Acidity in Humans

Abstract: This study examines 24‐hour gastric pH response under four nutritional conditions in 11 normal subjects. The conditions include: fasting, normal meals, and infusion of an equicaloric nutritional solution either parenterally or intraduodenally (i.d.). The volunteers underwent four 24‐hour intragastric pH measurement studies. Serum glucose, calcium, immunoreactive insulin, and gastrin levels were determined at various intervals. Median 24‐hour gastric pH values were significantly lower during i.d. infusion than during parenteral feeding but were not significantly different from fasting or normal diet values. Median 24‐hour serum glucose levels during i.d. infusion were higher than during fasting and lower than during parenteral nutrition. Median 24‐hour serum insulin levels during i.d. infusion were higher than during fasting but similar to levels during parenteral nutrition. Neither median 24‐hour gastrin levels nor calcium levels were altered by the various regimens. The authors conclude that continuous i.d. nutrient infusion produces gastric pH values similar to fasting or normal meal levels, whereas parenteral nutrition increases gastric pH. This suggests that under physiologic conditions, gastric acidity is under feedback control