Pylori-negative Healthy Volunteers Research Articles

Effect of Timing of Proton Pump Inhibitor Administration on Acid Suppression

Background: Esomeprazole has been reported to show a strong acid suppression following preprandial as compared to postprandial administration, though no known study has compared the acid suppressing effects of other proton pump inhibitors between those administrations. The aim of this study was to compare intragastric pH levels following pre- and postprandial administrations of rabeprazole and esomeprazole. Methods: In 15 Helicobacter pylori-negative healthy volunteers, we measured intragastric pH after 7 days of pre- and postprandial administrations of rabeprazole (10 mg) or esomeprazole (20 mg) using a 5-way crossover design. Results: Preprandial administration of esomeprazole showed stronger acid suppression than postprandial administration. The values for percent time at pH >4.0 over a 24-hour period increased from 45.3% with postprandial administration of esomeprazole to 54.4% with preprandial administration, while the percent time at pH >4.0 during daytime was increased to a greater extent from 51.4 to 66.5% with preprandial administration (p = 0.05). On the other hand, the acid suppressing effect of rabeprazole was not influenced by the timing of administration. Conclusions: The acid suppressing effect of esomeprazole is influenced by administration timing. In contrast, the acid suppressing effect of rabeprazole is not augmented by preprandial administration.

In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity

IntroductionRecently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine...

Reactive Increase in Gastric Mucus Secretion Is an Adaptive Defense Mechanism Against Low-Dose Aspirin-Induced Gastropathy

Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.

Helicobacter pylori infection and administration of non-steroidal anti-inflammatory drugs down-regulate the expression of gastrokine-1 in gastric mucosa

Gastrokine-1 is a novel protein that plays an important role in the maintenance of the integrity of the gastric mucosa. However, whether Helicobacter pylori infection and non-steroidal anti-inflammatory drugs, which are known to cause gastric mucosal injuries, affect gastrokine-1 expression in the gastric mucosa is unknown. The aim of the present study was to determine gastric mucosal expression of gastrokine-1 in patients with Helicobacter pylori infection or long-term non-steroidal anti-inflammatory drug administration. A total of 40 patients with functional dyspepsia (20 with Helicobacter pylori-negative chronic gastritis, and 20 with Helicobacter pylori-positive chronic gastritis), and 37 Helicobacter pylori-negative long-term non-steroidal anti-inflammatory drug users (26 with aspirin, 11 with selective cyclooxygenase-2 inhibitors) were selected. In addition, 20 Helicobacter pylori-negative healthy volunteers were recruited as controls. All subjects underwent endoscopies with biopsies taken from the antrum and the sites with lesions. Gastric mucosal changes were detected endoscopically and histologically, and gastrokine-1 protein expression in the antral mucosa was analyzed by immunohistochemistry. Expression of gastrokine-1 protein was decreased in Helicobacter pylori-positive chronic gastritis compared with Helicobacter pylori-negative subjects and the healthy controls. Similarly, gastrokine-1 expression in non-steroidal anti-inflammatory drug users was also decreased, compared with the healthy controls, but there was no significant difference in gastrokine-1 expression between the aspirin group and selective cyclooxygenase-2 inhibitor group. Moreover, gastrokine-1 expression levels tended to be associated with the severity of chronic gastritis. Both Helicobacter pylori infection and long-term non-steroidal anti-inflammatory drug administration downregulate gastrokine-1 expression in the gastric mucosa, which may contribute to the gastric mucosal injuries induced by these two factors.

PTU-176 Central obesity and age predict cardia mucosal length in healthy volunteers: evidence for an acquired entity

IntroductionOesophageal adenocarcinoma is thought to arise from columnar metaplasia of distal oesophageal mucosa caused by gastro-oesophageal reflux. Obesity is a risk factor for this process. There is some evidence that...

Tu1142 Central Obesity and Age Predict Cardia Mucosal Length in Healthy Volunteers: Evidence for an Acquired Entity

Introduction Oesophageal adenocarcinoma is thought to arise from columnar metaplasia of distal oesophageal mucosa caused by gastro-oesophageal reflux. Obesity is a risk factor for this process. There is some evidence that “normal” cardia may be an acquired mucosa arising through the same pathway and predisposing to adenocarcinoma development at this site. The influence of obesity on the aetiology of cardia mucosa is unknown. Methods 62 H pylori negative healthy volunteers (age 18–74 years) were recruited. BMI, waist circumference and gender were recorded. MRI (Phillips 1.5T) was performed for quantification of visceral and subcutaneous fat (average of three axial planes; L2, L3 and L4). Upper GI endoscopy was performed with biopsies of the gastrooesophageal junction. Biopsies were taken in a craniocaudal direction and targeted to include enough squamous mucosa to confirm position. Intra-procedure pathological feedback was available and two to three biopsies were taken to optimise accuracy. Junctional biopsies were assessed to determine cardia length, considered measurable provided there was consecutive squamous, cardia and oxyntic mucosal types present. Non-parametric correlations were examined between BMI, waist circumference and cardia length and between fat distribution quantified by MRI and cardia length. Regression analysis (Stepwise method) incorporating age, BMI, waist circumference and MRI total fat was used to determine predictors of cardia length. Results 37 of 62 volunteers had at least one junctional biopsy including squamous, cardia and oxyntic mucosa; median total length 6.5 mm (IQR 1.6). Median cardia mucosal length was 2.5 mm (IQR 1.5 mm). Length of cardia mucosa increased with age (R=0.457, p=0.004) and with waist circumference (R=0.466, p=0.004). A correlation was also seen with intra-abdominal fat (R=0.374, p=0.027) and total fat measured by MRI (R=0.389, p=0.021) but not with subcutaneous fat (p=0.091). There was no significant correlation with BMI. On regression analysis the independent predictors of cardia mucosa length were waist circumference (Standardised coefficient 0.342, p=0.035) and age (Standardised coefficient 0.322, p=0.046). Intestinal metaplasia at the cardia was seen in only 4 of 62 volunteers. Conclusion These findings suggest that cardia mucosa may be acquired with increasing age through a process of distal squamous columnar metaplasia accelerated by central obesity. A possible mechanism is opening of the distal portion of the lower oesophageal sphincter and short segment acid reflux. Competing interests None declared.

Acid inhibition effect of ilaprazole on Helicobacter pylori‐negative healthy volunteers: An open randomized cross‐over study

The aim of this study was to evaluate the effects and safety of different doses of ilaprazole on healthy volunteers without a Helicobacter pylori infection. A total of 12 healthy Chinese volunteers were enrolled and divided into four groups randomly, with a 5-day treatment of oral ilaprazole 5mg, 10mg and 20mg or omeprazole 20mg, respectively. After an interval of a 14-day washout phase, each was switched to another dose group and eventually completed all four regimens. The percentage time of intragastric pH>4 was the major index. The polymorphisms of the metabolic enzyme CYP2C19 in these volunteers were also detected. The percentage time of intragastric pH>4 in the ilaprazole 5, 10 and 20mg groups were 80.4%, 88.1% and 91.0%, respectively, during the first 24h, compared to that of the 20mg omeprazole group (76.6%, P>0.05). Ilaprazole 20mg provided a significant higher mean 24-h pH than that of the same dose of omeprazole both on Day 1 (7.78 vs 6.67, P<0.01) and Day 5 (7.95 vs 7.44, P<0.05). No CYP2C19-dependent difference or obvious adverse effect were found in any ilaprazole groups. Low dose ilaprazole offers a gastric acid inhibition comparable to a routine dose of omeprazole, and further investigations in patients with acid-associated diseases are needed.

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

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

Alu and Satα hypomethylation in Helicobacter pylori-infected gastric mucosae

Global hypomethylation and regional hypermethylation are supposed to be hallmarks of cancer cells. During gastric carcinogenesis, in which Helicobacter pylori infection is causally involved, aberrant hypermethylation is already present in H. pylori-infected gastric mucosae. In contrast, little is known about global hypomethylation, which can be caused by hypomethylation of individual repetitive elements and other sequences. We, therefore, investigated hypomethylation of individual repetitive elements and the global 5-methylcytosine content in four groups of gastric mucosal samples that represented the time course of H. pylori infection and gastric carcinogenesis [gastric mucosae of H. pylori-negative healthy volunteers (G1, n = 34), H. pylori-positive healthy volunteers (G2, n = 42), H. pylori-positive gastric cancer patients (G3, n = 34) and H. pylori-negative gastric cancer patients (G4, n = 20)] and 52 primary gastric cancers. Major variants of Alu, LINE1 and Satα were identified, and their methylation levels were quantified by bisulfite pyrosequencing. Compared with G1, the Alu methylation level was decreased in G2, G3, G4 and cancers (89.2-97.1% of that in G1, p < 0.05). The Satα methylation level was decreased in G2 (91.6%, p < 0.05) and G3 (94.3%, p = 0.08) but not in G4 and cancers. The LINE1 methylation level was decreased only in cancers. The 5-methylcytosine content was at similar levels in G2, G3 and G4 and highly variable in cancers. These results showed that Alu and Satα hypomethylation is induced in gastric mucosae by H. pylori infection during gastric carcinogenesis, possibly in different target cells, and that global hypomethylation is not always present in human gastric cancers.

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

T1141 Preventive Effect of Lansoprazole and Famotidine on Gastric Mucosal Injury Induced by Low-Dose Aspirin in H. pylori-Negative Healthy Volunteers

Background/Aims: Recent studies have revealed that interindividual differences in metabolic disposition of non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of NSAID-induced gastrointestinal mucosal injury. Individuals with poor metabolizer alleles of either or both CYP2C8 (such as CYP2C8*3) or CYP2C9 (such as CYP2C9*2 or CYP2C9*3), whichmetabolize NSAIDs, show increased risk of developing acute or chronic gastrointestinal injury on using NSAIDs. However, precise estimation of the metabolic profile of NSAIDs in an individual by combination of single nucleotide polymorphisms is difficult due to the variety of enzymes involved in NSAID metabolism. Given that 13CO2 is known to be produced on the metabolization of 13C-labeled naproxen ([13C]-naproxen), we examined whether or not the [13C]-naproxen breath test can be used to predict naproxen-induced gastric mucosal injury. Methods: Fifteen H. pylori-negative healthy volunteers (CYP2C9*1/ *1, n=13; CYP2C9*1/*3, n=2) ingested 300 mg of [13C]-naproxen, after which breath samples were collected over a period of 48 hours. Changes from baseline in carbon isotope ratios (13CO2/12CO2) in carbon dioxide were measured and expressed as a delta-overbaseline (DOB) ratio (‰), and plasma PGE2 and TXB2 were also measured at the same time. Gastric mucosal injury based on the modified Lanza score (MLS) was evaluated before and after twice daily dosing of naproxen 300 mg for 2 days. Results: At baseline, the median MLS was 0 (range: 0-1). After twice daily dosing with naproxen 300 mg for 2 days, however, MLS ranged from 1 to 5. Subjects were classified into one of three groups based on MLS level: patients with MLS of 1 or 2 were designated as mild (n = 5), MLS 3 as moderate (n = 7), and MLS 4 or 5 as severe (n =3). The AUC0-120min of DOB was 6.55 ± 0.31 h*‰ for the mild group, 5.45 ± 0.45) h*‰ for the moderate group, and 4.04 ± 0.97) h*‰ for the severe group; the AUC0-120min of DOB in the mild group was significantly higher than that in the severe group (P < 0.05). Overall, CYP2C9*1/*3 participants showed MLSs which fell in the severe group and had lower AUC0-120min of DOB values and lower rates of PGE2 and TXB2 than CYP2C9*1/*1 participants. Conclusion: [13C]-naproxen breath test results were significantly correlated with naproxen-induced mucosal injury, suggesting the usefulness of this test as a predictive determinant of naproxen-induced gastric mucosal injury.

T1144 Aggravation by Clopidogrel, the Antiplatelet Drug, of Antral Ulcers Induced by NSAIDs in Rats

Background/Aims: Recent studies have revealed that interindividual differences in metabolic disposition of non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of NSAID-induced gastrointestinal mucosal injury. Individuals with poor metabolizer alleles of either or both CYP2C8 (such as CYP2C8*3) or CYP2C9 (such as CYP2C9*2 or CYP2C9*3), whichmetabolize NSAIDs, show increased risk of developing acute or chronic gastrointestinal injury on using NSAIDs. However, precise estimation of the metabolic profile of NSAIDs in an individual by combination of single nucleotide polymorphisms is difficult due to the variety of enzymes involved in NSAID metabolism. Given that 13CO2 is known to be produced on the metabolization of 13C-labeled naproxen ([13C]-naproxen), we examined whether or not the [13C]-naproxen breath test can be used to predict naproxen-induced gastric mucosal injury. Methods: Fifteen H. pylori-negative healthy volunteers (CYP2C9*1/ *1, n=13; CYP2C9*1/*3, n=2) ingested 300 mg of [13C]-naproxen, after which breath samples were collected over a period of 48 hours. Changes from baseline in carbon isotope ratios (13CO2/12CO2) in carbon dioxide were measured and expressed as a delta-overbaseline (DOB) ratio (‰), and plasma PGE2 and TXB2 were also measured at the same time. Gastric mucosal injury based on the modified Lanza score (MLS) was evaluated before and after twice daily dosing of naproxen 300 mg for 2 days. Results: At baseline, the median MLS was 0 (range: 0-1). After twice daily dosing with naproxen 300 mg for 2 days, however, MLS ranged from 1 to 5. Subjects were classified into one of three groups based on MLS level: patients with MLS of 1 or 2 were designated as mild (n = 5), MLS 3 as moderate (n = 7), and MLS 4 or 5 as severe (n =3). The AUC0-120min of DOB was 6.55 ± 0.31 h*‰ for the mild group, 5.45 ± 0.45) h*‰ for the moderate group, and 4.04 ± 0.97) h*‰ for the severe group; the AUC0-120min of DOB in the mild group was significantly higher than that in the severe group (P < 0.05). Overall, CYP2C9*1/*3 participants showed MLSs which fell in the severe group and had lower AUC0-120min of DOB values and lower rates of PGE2 and TXB2 than CYP2C9*1/*1 participants. Conclusion: [13C]-naproxen breath test results were significantly correlated with naproxen-induced mucosal injury, suggesting the usefulness of this test as a predictive determinant of naproxen-induced gastric mucosal injury.

T1140 Usefulness of the [13C]-Naproxen Breath Test in Predicting Naproxen-Induced Gastric Mucosal Injury

Background/Aims: Recent studies have revealed that interindividual differences in metabolic disposition of non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of NSAID-induced gastrointestinal mucosal injury. Individuals with poor metabolizer alleles of either or both CYP2C8 (such as CYP2C8*3) or CYP2C9 (such as CYP2C9*2 or CYP2C9*3), whichmetabolize NSAIDs, show increased risk of developing acute or chronic gastrointestinal injury on using NSAIDs. However, precise estimation of the metabolic profile of NSAIDs in an individual by combination of single nucleotide polymorphisms is difficult due to the variety of enzymes involved in NSAID metabolism. Given that 13CO2 is known to be produced on the metabolization of 13C-labeled naproxen ([13C]-naproxen), we examined whether or not the [13C]-naproxen breath test can be used to predict naproxen-induced gastric mucosal injury. Methods: Fifteen H. pylori-negative healthy volunteers (CYP2C9*1/ *1, n=13; CYP2C9*1/*3, n=2) ingested 300 mg of [13C]-naproxen, after which breath samples were collected over a period of 48 hours. Changes from baseline in carbon isotope ratios (13CO2/12CO2) in carbon dioxide were measured and expressed as a delta-overbaseline (DOB) ratio (‰), and plasma PGE2 and TXB2 were also measured at the same time. Gastric mucosal injury based on the modified Lanza score (MLS) was evaluated before and after twice daily dosing of naproxen 300 mg for 2 days. Results: At baseline, the median MLS was 0 (range: 0-1). After twice daily dosing with naproxen 300 mg for 2 days, however, MLS ranged from 1 to 5. Subjects were classified into one of three groups based on MLS level: patients with MLS of 1 or 2 were designated as mild (n = 5), MLS 3 as moderate (n = 7), and MLS 4 or 5 as severe (n =3). The AUC0-120min of DOB was 6.55 ± 0.31 h*‰ for the mild group, 5.45 ± 0.45) h*‰ for the moderate group, and 4.04 ± 0.97) h*‰ for the severe group; the AUC0-120min of DOB in the mild group was significantly higher than that in the severe group (P < 0.05). Overall, CYP2C9*1/*3 participants showed MLSs which fell in the severe group and had lower AUC0-120min of DOB values and lower rates of PGE2 and TXB2 than CYP2C9*1/*1 participants. Conclusion: [13C]-naproxen breath test results were significantly correlated with naproxen-induced mucosal injury, suggesting the usefulness of this test as a predictive determinant of naproxen-induced gastric mucosal injury.

Immediate acid‐suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross‐over study using wireless pH monitoring capsules

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Rebamipide, a Cytoprotective Drug, Increases Gastric Mucus Secretion in Human: Evaluations with Endoscopic Gastrin Test

We have previously developed a rapid, simple endoscopic method for evaluating gastrin-stimulated maximal acid output (the endoscopic gastrin test, EGT). In EGT, gastric fluid newly secreted over 10 min after gastrin stimulation is collected under direct endoscopic visualization. In this study, employing the EGT, we evaluated the effect of rebamipide, a cytoprotective anti-ulcer drug, on gastric mucus secretion. In ten Helicobacter pylori-negative healthy volunteers, gastric juice was collected by EGT prior to and after 4-week administration of rebamipide. The collected gastric juice was subjected to analysis for gastric mucus output. Total gastric mucin output was significantly increased by 53% by rebamipide administration from 3.2 ± 1.2 mg hexose/10 min to 4.9 ± 2.2 mg hexose/10 min (P < 0.01). Further analysis by ion-exchange chromatography revealed that rebamipide administration induced a specific increase in acidic mucin rich in sialic acid. Applying EGT, this study demonstrated that rebamipide administration increased gastric mucus secretion in human.

Prevention of Indomethacin-Induced Gastric Mucosal Injury in Helicobacter pylori-Negative Healthy Volunteers: A Comparison Study Rebamipide vs Famotidine

The clinical efficacy of gastroprotective drugs or low-dose H2 receptor antagonists in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy is limited. The aim of the present study was to investigate efficacy of rebamipide and famotidine in Helicobacter pylori (H. pylori)-negative healthy volunteers taking NSAID. This study was a randomized, two way crossover study comparing the preventive effect rebamipide 100 mg, t.i.d. and famotidine 10 mg, b.i.d against indomethacin (25 mg, t.i.d.)-induced gastric mucosal injury in H. pylori-negative healthy volunteers. 12 subjects satisfied criteria and were randomized. Endoscopy was performed at baseline and again after the treatment for 7 days, and symptoms were recorded during the treatment. Tissue levels of lipid peroxides and myeloperoxidase and serum indomethacin concentrations were also measured. Subjective symptoms were developed in 58% (7/12) of the rebamipide group, and in 75% (9/12) of the famotidine group (no significant differences). The incidence of gastric lesions (modified Lanza score 2 or higher) was 17% (2/12) in the rebamipide group and 25% (3/12) in the famotidine group. Peptic ulcers did not occur in both groups. There were no significant differences in tissue levels of lipid peroxide and myeloperoxidase and serum level of indomethacin between two groups after the treatment. In conclusion, these data recommend rebamipide (100 mg, t.i.d.) or famotidine (10 mg, b.i.d.) for the prevention of acute gastric injury induced by NSAID in patients without a particular risk factor.

Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24‐h intragastric pH in healthy volunteers

To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori-negative healthy volunteers. Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days' dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days' dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were > or =14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5. Single doses of rabeprazole 20 mg maintained 24-h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days' dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0-5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night. The order of effects on 24-h pH was: rabeprazole 10 mg < or = esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer.

Oral Rabeprazole 20 Mg Provides More Effective Acid Control Than IV Pantoprazole 40 Mg

Purpose: Intravenous (IV) proton-pump inhibitor therapy is used increasingly in hospitalized patients, even if, in many cases, they can take oral medication. Oral and IV pantoprazole produce equivalent acid suppression; oral rabeprazole produces greater acid suppression than oral pantoprazole. This study compares the antisecretory effects (time pH>3, 4, 5 & 6) produced by standard doses of oral rabeprazole and IV pantoprazole in healthy volunteers. Methods: Double-blind, randomized, two-way crossover study in 38 Helicobacter pylori-negative healthy volunteers. Subjects received oral rabeprazole 20 mg or IV pantoprazole 40 mg once daily for 3 days, with a 14-day (±3) washout period before the second 3-day drug administration period with the crossover drug regimen. Intragastric pH was recorded continuously for a 24-h period after dosing on days 1 and 3 of each treatment phase. Results: Over a 24-hour period, oral rabeprazole produced greater acid suppression than IV pantoprazole on day 1 [pH>3.0 (51.0%, 35.7%; p < 0.001), pH>4.0 (37.7%, 23.9%; p < 0.001), pH>5.0 (24.9%, 14.2%; p < 0.001), pH>6.0 (11.2%, 5.8%; p= 0.024)] and on day 3 [pH>3.0 (68.4%, 51.5%; p < 0.0001), pH>4.0 (54.4%, 37.7%; p < 0.001), pH>5.0 (38.1%, 24.8%; p <0.001), pH>6.0 (17.3%, 11.5%; p= 0.017)]. Over a 10-hour night-time period, oral rabeprazole produced greater acid suppression than IV pantoprazole on day 1 [pH>3.0 (42.8%, 27.8%; p < 0.010), pH>4.0 (30.2%, 18.2%; p= 0.017)] and on day 3 [pH>3 (56.2%, 37.0%; p < 0.001), pH>4 (43.4%, 26.2%; p= <0.002), pH>5 (29.8%, 18.8%; p= 0.024). Conclusions: In healthy subjects, oral rabeprazole provides greater intragastric acid suppression over 24 hours and during the 10-hour nocturnal period on day 1 and 3 than IV pantoprazole. Oral rabeprazole may be an appropriate substitute for IV pantoprazole in patients who can take oral medication. [figure 1]Figure 1

Lansoprazole regimens that sustain intragastric pH &gt;6.0: an evaluation of intermittent oral and continuous intravenous infusion dosages

Orally and intravenously administered proton pump inhibitors have been shown to reduce rebleeding rates, surgery and transfusion requirement. To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid SoluTab) regimens with a pantoprazole intravenously administered regimen in sustaining intragastric pH >6.0. Two similarly designed three-way, randomized crossover studies each enrolled 36 Helicobacter pylori-negative healthy volunteers. Study 1 regimens included intravenously administered bolus followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole 120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included intravenous bolus followed by lansoprazole orally disintegrating tablet or intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole 80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH monitoring. All regimens produced comparable gastric acid suppression. In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6-mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s. and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h regimen (P = 0.082) was not superior to pantoprazole in percentage of time intragastric pH >6.0. Mild reaction at the intravenous injection site was the most frequently reported adverse event. The intravenous bolus and continuously infused lansoprazole or intravenous bolus and intermittent lansoprazole orally disintegrating tablet regimens are as effective as intravenous pantoprazole in sustaining intragastric pH >6.0.

The effect of single‐dose naproxen on eicosanoid formation in human gastroduodenal mucosa

In animal studies, aspirin and non-aspirin non-steroidal anti-inflammatory drugs contribute to gastroduodenal damage via cyclo-oxygenase inhibition and consecutive leucotriene formation (COX-LOX eicosanoid shunt). Ten Helicobacter pylori-negative healthy volunteers received a single dose of 500 mg naproxen to address two questions: (i) is there a crosstalk between eicosanoids before medication in the human gastroduodenal mucosa and (ii) can we demonstrate a COX-LOX shunt following single-dose naproxen? Significant correlations in the stomach mucosa before medication were obtained between leucotriene B4 (LTB4) and thromboxane B(2) (TxB(2); r = -0.38, P = 0.05), as well as LTB4 and prostaglandin E(2) (PGE(2); r = 0.71, P < 0.0001). In serum, a >90% inhibition of TxB(2) and PGE(2) occurred within 30 min of naproxen administration. In gastric mucosa, a significant decrease of TxB(2) occurred already at 15 min and preferably in the antrum. For LTB4 there was a non-significant trend towards a transient increase. Mucosal PGE(2) was unchanged in all regions; transcript levels of both cyclo-oxygenases/5-lipoxygenase were unaffected (except for a trend of increasing cyclo-oxygenase-2 in the corpus). Baseline correlations between LTB4-TxB(2) and LTB4-PGE(2) reflect a crosstalk between these eicosanoids. A COX-LOX shunt; however, cannot be demonstrated following single-dose naproxen in a low-risk population.