Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole.

It has been shown that omeprazole treatment produces higher intragastric pH values in Helicobacter pylori positive subjects than in H pylori negative subjects. This study aimed to investigate the effect of curing H pylori on the intragastric pH in both the presence and absence of omeprazole therapy. Twenty four hour intragastric pH recordings were performed before and after a one week course of omeprazole (20 mg once daily) in 18 H pylori positive subjects and were repeated after the infection had been cured. In the absence of omeprazole, the total 24 hour pH values before cure did not differ from those afterwards. During omeprazole treatment the 24 hour pH values were much higher before (median (95% CI) 5.4: 4.3, 6.0), than after cure of infection (3.6: 2.1, 4.4; p < 0.001). The omeprazole induced fall in H+ activity before cure of H pylori did not, however, differ from that afterwards. It is concluded that the apparently greater antisecretory effect of omeprazole during H pylori infection may be a result of the production of acid neutralising compounds by the H pylori. Although a direct interaction between H pylori and omeprazole cannot be excluded, it seems unlikely.     

Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole.

Omeprazole is a powerful inhibitor of gastric acid and may suppress Helicobacter pylori by effecting the pKa of H pylori urease, by altering the pattern of infection, or by promoting overgrowth of other bacteria. At routine endoscopy H pylori was detected by histology and culture before and after four weeks' treatment with omeprazole, 40 mg each morning. A 13C-urea breath test was also done at t = 0, 2, 4, and 6 weeks. Thirty nine patients with duodenal ulcer (n = 25) or reflux oesophagitis (n = 14) were studied, of whom 29 of 39 had H pylori infection. During omeprazole treatment, 13C-urea breath test values fell significantly--mean (SEM) values before treatment and at four weeks were 23.0 (2.1) and 15.5 (2.7) per mil respectively, p < 0.001. Before treatment H pylori was seen in 28 of 29 antral, 29 of 29 corpus, and 28 of 29 fundic biopsy specimens. After four weeks of omeprazole treatment, the histological density of H pylori in the antrum and corpus was reduced (p < 0.001), while that in the fundus was increased. The migration of H pylori from the antrum to the fundus was associated with a corresponding decrease in the activity of antral gastritis. H pylori was not seen in antral biopsy specimens from 12 of 29 patients whose median excess delta 13CO2 excretion fell from 23.0 to 9.9 per mil. In the body mucosa, 26 of 29 specimens were still positive for H pylori and there was no significant change in the gastritis type. Two weeks after finishing treatment, the mean (SEM) excess delta 13CO2 excretion returned to levels before treatment. Omeprazole decreases antral H pylori colonisation but increases that in the fundus. The changes in the intragastric distribution of the organism are associated with concomitant changes in the activity of gastritis and are matched by a progressive fall in the excretion of delta 13CO2.     

Effect of Helicobacter pylori status on intragastric pH during administration of lafutidine or famotidine

BACKGROUND/AIMS: There has been no study attempting to compare the effects of lafutidine, a novel H2-receptor antagonist and other H2-receptor antagonists in the same subjects and relating them to H. pylori status. The first aim of this study was to investigate the effect of H. pylori status on intragastric pH in healthy volunteers receiving lafutidine or famotidine. The second aim was to compare the effects of the two antisecretory drugs. METHODOLOGY: The study was carried out in 11 healthy asymptomatic male volunteers. H. pylori infection was present in 5 subjects. Subjects were first examined by an ambulatory pH monitoring for 24 hours without medication. The second and third 24-hour pH monitoring study was performed on all subjects. Subjects took 10 mg lafutidine or 20mg famotidine at 9:00 and 21:00. RESULTS: During administration of lafutidine or famotidine, the percentage of period holding intragastric pH >4 was not significantly different between the H. pylori-negative and -positive subjects. Among the H. pylori negative subjects, the percentage of daytime period holding intragastric pH >4 was significantly greater with lafutidine than with famotidine (p < 0.05). CONCLUSIONS: The effect of lafutidine to increase intragastric pH was not affected by the H. pylori status. Among H. pylori-negative subjects, lafutidine was proven to be more effective than famotidine for acid control during the daytime in Japanese healthy volunteers.     

Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole

BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. METHODS: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.     

Effect of curing Helicobacter pylori infection on intragastric acidity during treatment with ranitidine in patients with duodenal ulcer.

BACKGROUND: In patients with duodenal ulcer cure of Helicobacter pylori infection resulted in a pronounced decrease in intragastric pH during treatment with omeprazole. AIM: To test the hypothesis that treatment of H pylori adversely affects the pH response to ranitidine. PATIENTS: Eighteen patients with duodenal ulcer who were infected with H pylori were studied. METHODS: Twenty four hour pH recordings were performed during treatment with ranitidine (300 mg) at night before and four to six weeks after cure of H pylori infection. Presence of H pylori was assessed by a rapid urease test, culture, histology, and a 13C urea breath test. Also, the fasting gastrin concentrations were measured before and after treatment for H pylori infection. RESULTS: Cure of H pylori infection resulted in a considerable improvement in both antral and corpus gastritis and a decrease in fasting gastrin concentrations. As a result of the cure the night time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v 5.4; p = 0.007), whereas the acidity during the daytime was not affected. CONCLUSIONS: In patients with duodenal ulcer the intragastric pH during treatment with ranitidine depends on H pylori. However, the loss of effectiveness in altering pH seems to be less pronounced than previously found with omeprazole.     

Elimination of Helicobacter pylori under treatment with omeprazole

Biopsies from the stomachs (antrum and corpus) of 201 patients with peptic ulcers or reflux oesophagitis were retrospectively investigated for the effect of treatment with omeprazole on the elimination of Helicobacter pylori (HP) and on gastritis. Of 64 patients without gastritis two (3.1%) developed gastritis during treatment. Among 134 patients with HP gastritis undergoing treatment, 48 (35.8%) experienced no HP elimination, in 41 (30.6%) there was HP elimination from the antrum, but HP persistence in the corpus, while in 45 (33.6%) HP was eliminated from both antrum and corpus. HP elimination led to a reduction in the degree and activity of gastritis under omeprazole treatment. Only eight patients were examined after completion of treatment, and in three in whom HP had been eliminated, recolonization was found to have occurred. The disappearance of HP in Type A gastritis coupled with the fact that HP is highly sensitive to contamination with other bacteria--as observed in the laboratory--suggests that this now partially established elimination of HP under the strongly acid-inhibiting omeprazole therapy can be traced back to a bacterial overgrowth of the gastric mucosa.     

Effect of intravenous omeprazole on intragastric pH during intravenous infusion of amino acids

Intravenous amino acids stimulate gastric acid secretion by an unknown mechanism. In patients on parenteral nutrition, this amino acid-induced gastric acid secretion might contribute to the failure of H₂-receptor antagonists to raise intragastric pH above 4.0, a level thought to be needed to prevent stress ulceration. Therefore we studied the effect of single and repeated doses of the H⁺/K⁺-ATPase blocker omeprazole on the intragastric pH during a 3-hr infusion of amino acids in 10 healthy volunteers; 5% glucose was used as a control infusion. Amino acids significantly decreased intragastric pH when compared to glucose infusion (P <0.05). After intravenous administration of 40 mg, 80 mg and 2 × 40 mg omeprazole, this amino acid-induced fall in pH was significantly inhibited (P < 0.01). No advantage of the 80-mg dose over the 40-mg dose could be demonstrated. The repeated dose of 40 mg showed a tendency to higher pH values compared to the single-dose experiments, which reached significance in the amino acid experiments only (P <0.05). Neither during the infusion of amino acids nor the glucose infusion omeprazole was able to continuously raise intragastric pH above 4.0. In conclusion, this study shows that intravenous omeprazole prevents gastric acid stimulation by intravenous amino acids but fails to continuously raise intragastric pH above 4.     

Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy

BACKGROUND: We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. AIM: To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. PATIENTS/METHODS: In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. RESULTS: In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p相似文献   

Intravenous omeprazole rapidly raises intragastric pH.

Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound.     

Eradicating Helicobacter pylori reduces hypergastrinaemia during long term omeprazole treatment

Background—Both proton pump inhibitor drugtreatment and Helicobacter pylori infection causehypergastrinaemia in man.
Aims—To determine whether eradicating Hpylori is a means of reducing hypergastrinaemia duringsubsequent proton pump inhibitor treatment.
Methods—Patients with H pylori wererandomised to treatment with either anti-H pylori orsymptomatic treatment. One month later, all received four weekstreatment with omeprazole 40 mg/day for one month followed by 20 mg/dayfor six months. Serum gastrin concentrations were measured before andfollowing each treatment.
Results—In the patients randomised toanti-H pylori treatment, eradication of the infectionlowered median fasting gastrin by 48% and meal stimulated gastrin by46%. When gastrin concentrations one month following anti-Hpylori/symptomatic treatment were used as baseline,omeprazole treatment produced a similar percentage increase in serumgastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing amedian increase of 68% (p<0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrinat initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95).
Conclusion—Eradicating H pylori is ameans of reducing the rise in gastrin during subsequent long termomeprazole treatment. In view of the potential deleterious effects ofhypergastrinaemia it may be appropriate to render patients Hpylori negative prior to commencing long term proton pumpinhibitor treatment.

Keywords:hypergastrinaemia; Helicobacter pylori; omeprazole

     

Eradication of Helicobacter pylori with clarithromycin and omeprazole.

Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03 microgram/l-1) against Helicobacter pylori (H pylori). This study aimed at determining the eradication rate using clarithromycin 500 mg thrice daily and omeprazole 40 mg daily for two weeks. Patients were given an endoscopy and H pylori status assessed by antral culture (microaerobic conditions, for up to 10 days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains), and 13C-urea breath test (13C-UBT, European standard protocol, positive result = excess delta 13CO2 excretion > 5 per mil). Compliance was assessed by returned tablet counts. H pylori clearance at the end of treatment and eradication four weeks after finishing treatment were assessed by the 13C-UBT. Seventy three patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM) excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral histology (n = 72) or positive antral culture (n = 35) were studied. Before treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and five isolates were resistant to metronidazole. In 70/73 (96%) the 13C-UBT was negative immediately after finishing treatment. Four weeks later the 13C-UBT was negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil, eradication rate = 78%). Forty eight (66%) patients experienced a metallic taste while taking the tablets. Although four (5%) patients, however, could not complete the course of treatment, in only one of these four was H pylori not eradicated. These results show that duel therapy with clarithromycin and omeprazole is well tolerated. With an eradication rate of 78% it is an effective treatment for metronidazole resistant H pylori and may be an alternative to standard triple therapy.     

Two weeks treatment with amoxicillin/omeprazole for eradication of Helicobacter pylori.

In an open study, 62 patients with Helicobacter pylori-associated ulcer disease or functional dyspepsia were treated for two weeks with 2 x 20 mg omeprazole preprandially and 4 x 500 mg amoxicillin suspension one hour before meals and at night. 57 patients (active ulcer disease: n = 53, functional dyspepsia: n = 4) completed the study without contravening the protocol. The rate of eradication of the bacteria at least 4 weeks after cessation of study medication was 82.5% (47/57 patients). Three patients experienced side effects during the treatment period (stomatitis, self-limiting diarrhea, allergic exanthema). In one case allergic exanthema led to discontinuation of therapy. 11 patients with H. pylori-associated ulcer disease received 2 x 20 mg omeprazole for two weeks. In this group no eradication of bacteria was observed.     

Effect of Helicobacter pylori infection on intragastric acidity in patients with reflux esophagitis

Background The effect of Helicobacter pylori infection on intragastric acidity in patients with reflux esophagitis was investigated.Methods Esophageal motility and 24-h intragastric acidity were assessed in endoscopy-proven reflux esophagitis patients with (n = 50) and without (n = 50) H. pylori infection.Results Most of the patients had a mild degree of esophagitis. There was no difference in the age, sex, or body mass index (BMI) between patients with and without H. pylori infection. The 24-h intragastric pH monitoring showed less acidity in patients with H. pylori infection than in those without H. pylori infection (median pH, 1.6 ± 0.3 vs 1.4 ± 0.1, with vs without H. pylori infection; P < 0.01). No difference in the patterns of esophageal motility dysfunction was noted between these two groups of patients.Conclusions Patients with reflux esophagitis and H. pylori infection had less intragastric acidity than those without H. pylori infection. However, the extent of acid suppression was insufficient to protect the esophagus from acid injury. In addition, the degree of esophageal motility dysfunction was similar in both groups. Therefore, H. pylori infection may play no role in the pathogenesis of reflux esophagitis.     

The effect of intragastric acidity on Helicobacter pylori eradication with bismuth-metronidazole-amoxicillin.

BACKGROUND/AIMS: Adding an acid secretion inhibitor to anti-H. pylori regimens may be potentially valuable for enhancing the effectiveness of antimicrobials that exhibit markedly reduced activity at low pH. This study was conducted to evaluate intragastric acidity as a factor in H. pylori eradication with bismuth-based triple therapy. METHODOLOGY: Forty patients with duodenal ulcer and H. pylori infection were included. The patients were divided into 2 groups--normacid (n = 20) and hyperacid (n = 20)--based on the amount of time that 24-hour intragastric pH took to reach the level pH > or = 3. All patients received bismuth subsalicylate (600 mg 3 times daily), metronidazole (500 mg 3 times daily) and amoxicillin (500 mg 3 times daily) for 2 weeks. Then, all patients continued treatment with ranitidine (150 mg twice daily) for 8 weeks prior to the follow-up examination. Blood samples were collected before treatment for measurement of fasting gastrin and pepsinogen-I. RESULTS: Nine patients (45%) in the normacid group and 8 patients (40%) in the hyperacid group reported side effects. However, there were only 2 patients (10%) in each group who withdrew from the study due to intolerance of side-effects. There was no difference in the H. pylori eradication rate between the normacid and hyperacid groups (16/18, 88.9% vs. 15/18, 83.3%). CONCLUSIONS: Without co-administration of anti-secretary agents, intragastric acid is not a significant factor in the effectiveness of H. pylori eradication with bismuth-based triple therapy.     

Pylera plus omeprazole: quadruple treatment for Helicobacter pylori

In 2007, the American College of Gastroenterology published updated treatment guidelines for the management of Helicobacter pylori infection, the leading cause of peptic ulcers. The recommended effective therapies are a triple drug regimen for 14 days or a quadruple bismuth therapy for 10 to 14 days, which includes a combination of a proton pump inhibitor such as omeprazole, bismuth, metronidazole, and tetracycline. These drug regimens all require strict adherence and several pills daily, but recent formulations have lessened the pill burden, which can improve patient compliance and outcomes. The pharmacology, product availability, efficacy, and potential adverse reactions of these regimens are discussed in this review.     

Effect of omeprazole on nocturnal intragastric pH in cirrhotics with inadequate antisecretory response to ranitidine

Failure of acid suppression by H2-receptor antagonists has been observed, and recently we have found a higher frequency of patients with inadequate antisecretory response among patients with cirrhosis of the liver. In the present study comprising 16 cirrhotics with inadequate antisecretory response to 300 mg of ranitidine, we tested the effect of 40 mg omeprazole. Nighttime intragastric pH was continuously monitored, and a rise in the intragastric pH above 4.0 for more than 6 h following the oral dose at 18.00 h was considered as response. The median pH profile during the omeprazole treatment was significantly higher than with ranitidine (p less than or equal to 0.001). In contrast to 300 mg ranitidine, which despite sufficient plasma levels 2 and 4 h after intake (762 +/- 431 and 802 +/- 668 ng/ml) resulted in a rise in the nighttime intragastric pH above 4 only for 1.8 +/- 1.7 h, after omeprazole for at least 5 days, the intragastric pH was for 10.1 +/- 2.4 of 12 h above 4 during the night (p less than 0.001). The omeprazole plasma levels were 611 +/- 323 and 881 +/- 533 ng/ml after 2 and 4 h. The data obtained with intragastric pH monitoring indicate that the H+K(+)-ATPase inhibitor omeprazole is able to overcome the H2-blocker resistance in cirrhotics.     

Rapid effect of lansoprazole on intragastric pH: a crossover comparison with omeprazole.

BACKGROUND: The time to onset of acid inhibition is considered an important factor when treating patients with reflux symptoms. This study was therefore designed to investigate the effect of 30 mg lansoprazole and 20 mg omeprazole on gastric pH after single-dose administration. METHODS: The study was of a randomized, open-label, single-dose and two-way crossover design with a washout period of at least 7 days in between. Fifteen healthy adult male and female subjects were included. The subjects were intubated with a pH catheter. Intragastric pH was measured every 4th sec for 10 min before and during 8 h after drug administration. Blood samples, for determination of plasma concentrations of lansoprazole and omeprazole, were obtained on 10 occasions during 6 h after drug administration. The area under the curve (AUC), the elimination halflife (t1/2), and the peak concentration (Cmax) of the two drugs were calculated. RESULTS: All subjects completed the study without major complications. The mean pH (0-8 h) after drug administration was 2.9 for lansoprazole and 2.0 for omeprazole (P = 0.0058). A pH of more than 4 was reached for the first time after 130 min with lansoprazole and after 250 min with omeprazole. AUC was 4919 +/- 2526 nmol/l x h for lansoprazole and 1352 +/- 1120 nmol/l x h for omeprazole. CONCLUSION: Single-dose administration of 30 mg lansoprazole is followed by a rapid absorption of the drug and hence a more efficient acid suppression than after single-dose administration of 20 mg omeprazole in healthy volunteers.     

Effect of Helicobacter pylori Infection on Gastric Juice pH

Background: How Helicobacter pylori infection affects gastric acid secretion is still unclear. Methods: Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls. Results: Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed. Conclusions: These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.