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Biochemistry. Biokhimiia Jul 2000Zinc complex of L-carnosine (L-CAZ; generic name Polaprezinc) is the first drug for oral administration in which zinc plays an essential role. L-CAZ was approved as an... (Review)
Review
Zinc complex of L-carnosine (L-CAZ; generic name Polaprezinc) is the first drug for oral administration in which zinc plays an essential role. L-CAZ was approved as an anti-ulcer drug of membrane protection type. Characterization of L-CAZ was achieved by various spectroscopic methods along with elemental analysis. Zinc ion coordinates with L-carnosine to form a quadridentate 1:1 complex of polymeric nature in order to maintain low strain of chelate rings. L-CAZ can remain in stomach juice without rapid dissociation and adhere to ulcerous lesion specifically, after which L-carnosine and zinc are released to heal the ulcer. L-CAZ exhibited high efficacy in clinical use without any serious side effect. L-CAZ exhibited an inhibitory effect on Helicobacter pylori. Physicochemical aspects on carnosine, zinc, and zinc complex can explain favorable features of L-CAZ as a drug.
Topics: Animals; Anti-Ulcer Agents; Carnosine; Helicobacter pylori; Magnetic Resonance Spectroscopy; Mass Spectrometry; Organometallic Compounds; Rats; Zinc; Zinc Compounds
PubMed: 10951100
DOI: No ID Found -
Nature Communications Jul 2019Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy...
Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy incidence at a population level remains uncharacterized. Here we aim to assess the use of anti-allergic medication following prescription of gastric acid inhibitors. We analyze data from health insurance records covering 97% of Austrian population between 2009 and 2013 on prescriptions of gastric acid inhibitors, anti-allergic drugs, or other commonly prescribed (lipid-modifying and antihypertensive) drugs as controls. Here we show that rate ratios for anti-allergic following gastric acid-inhibiting drug prescriptions are 1.96 (95%CI:1.95-1.97) and 3.07 (95%-CI:2.89-3.27) in an overall and regional Austrian dataset. These findings are more prominent in women and occur for all assessed gastric acid-inhibiting substances. Rate ratios increase from 1.47 (95%CI:1.45-1.49) in subjects <20 years, to 5.20 (95%-CI:5.15-5.25) in > 60 year olds. We report an epidemiologic relationship between gastric acid-suppression and development of allergic symptoms.
Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Austria; Female; Gastric Acid; Humans; Hypersensitivity; Immune System; Incidence; Male; Medical Records; Middle Aged; Proton Pump Inhibitors; Young Adult
PubMed: 31363098
DOI: 10.1038/s41467-019-10914-6 -
Alimentary Pharmacology & Therapeutics Feb 2003Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the... (Review)
Review
Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the systemic circulation, compared with an equal dose of omeprazole. Also, this superior delivery has been shown to cause a more consistent and greater suppression of pentagastrin-stimulated gastric acid secretion by esomeprazole, 20 mg, compared with omeprazole, 20 mg. The superior acid-suppressant properties of esomeprazole have been revealed by extensive 24-h intragastric pH-monitoring studies. Compared with omeprazole, 20 mg, esomeprazole, 20 mg and 40 mg, has been shown to give superior outcomes on three key measures of antisecretory effect: (1) consistency amongst individuals; (2) duration over the 24-h cycle; (3) overall impact on pH. As there is a substantial increment of acid control from esomeprazole, 20 mg, to esomeprazole, 40 mg, this latter dose is the most appropriate to investigate for modern initial therapy of reflux disease, with the aim of achieving the highest possible response rates in the shortest possible time.
Topics: Anti-Ulcer Agents; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Omeprazole; Pentagastrin; Proton Pump Inhibitors
PubMed: 12614299
DOI: 10.1046/j.1365-2036.17.s1.2.x -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Nov 2019Perforation is a rare complication of peptic ulcer. Although the most widely accepted treatment for peptic ulcer perforation is surgery, non-operative treatment can be...
BACKGROUND
Perforation is a rare complication of peptic ulcer. Although the most widely accepted treatment for peptic ulcer perforation is surgery, non-operative treatment can be an option in selected patients. In this study, we aimed to present our non-surgical treatment experience in peptic ulcer perforation.
METHODS
In this study, the data of the patients who were treated due to peptic ulcer perforation between January 2012 and September 2017 in our clinic were retrospectively reviewed. The diagnosis was reached by physical examination and radiologic findings. After obtaining the informed consent from the patients, non-operative treatment was performed to the selected patients who had normal vital parameters and did not have findings of generalized peritonitis in the abdominal examination. Oral food and fluid intake were stopped and intravenous fluid, antibiotics and pantoprazole were administered to all patients in this study.
RESULTS
A total of 41 patients were treated due to the diagnosis of peptic ulcer perforation in our clinic during the study period. Out of 41 patients, while 35 of the patients were operated, six of them were treated non-operatively. There were peritoneal irritation signs and symptoms in the upper quadrants on physical examination in all of the patients. None of them had generalized peritonitis. Abdominal X-ray and computed tomography were obtained from all of the patients. None of the patients in the non-operative group underwent any interventional procedure or surgery during the follow-up period. The median length of hospital stay was four days in this group. All of the patients were discharged uneventfully.
CONCLUSION
Standard treatment of peptic ulcer perforation in most of the patients is still surgical repair. Non-surgical treatment should be kept in mind as an option in the selected patients who had normal vital parameters and did not have any findings of generalized peritonitis in the abdominal examination. In this way, it may be possible to avoid unnecessary surgery and reduce the possible morbidity and mortality associated with the operation.
Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Fluid Therapy; Humans; Length of Stay; Pantoprazole; Peptic Ulcer Perforation; Peritonitis; Retrospective Studies
PubMed: 31701498
DOI: 10.14744/tjtes.2019.31967 -
Drug Delivery Aug 2021Nizatidine (NIZ), a histamine H-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore,...
Nizatidine (NIZ), a histamine H-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore, chitosan (CS) and polyethylene oxide (PEO) nanofibers (NFs) at different weight ratios were prepared by electrospinning and characterized. The selected uncrosslinked and glutaraldehyde-crosslinked NFs were investigated regarding floating, solid-state characteristics, release, and cytotoxicity. The cytoprotective activity against ethanol-induced gastric injury in rats was evaluated through macroscopical, histopathological, immunohistochemical, and oxidative stress examinations. NFs based on 8:2 CS:PEO exhibited the smallest diameter (119.17 ± 22.05 nm) and the greatest mucoadhesion (22.82 ± 3.21 g/cm), so they were crosslinked with glutaraldehyde. Solid-state characterization indicated polymers interaction, a successful crosslinking, and NIZ dispersion in NFs. Crosslinking maintained swollen mats at pH 1.2 (swelling% = 29.47 ± 3.50% at 24 h), retarded their erosion at pH 6.8 (swelling%= 84.64 ± 4.91% vs. 25.40 ± 0.79% for the uncrosslinked NFs at 24 h), augmented the floating up to 24 h vs. 10 min for the uncrosslinked NFs at pH 1.2 and prolonged the drug release (%drug released ≥ 93% at 24 h vs. 4 and 5 h for the uncrosslinked NFs at pHs 1.2 and 6.8, respectively). The viability of Caco-2 cells ≥ 86.87 ± 6.86% revealed NFs biocompatibility and unreacted glutaraldehyde removal. Crosslinking of 8:2 CS:PEO NFs potentiated the antiulcer activity (38.98 vs. 8.67 for the uncrosslinked NFs) as well as it preserved the gastric wall architecture, COX-2 expression, and oxidative stress markers levels of the normal rats.
Topics: Animals; Anti-Ulcer Agents; Caco-2 Cells; Cell Survival; Chemistry, Pharmaceutical; Chitosan; Drug Carriers; Drug Liberation; Glutaral; Humans; Hydrogen-Ion Concentration; Nanofibers; Nizatidine; Polyethylene Glycols; Random Allocation; Rats
PubMed: 34470551
DOI: 10.1080/10717544.2021.1971796 -
Journal of Veterinary Internal Medicine Mar 2019Although the demand for esomeprazole is increasing in veterinary medicine, the pharmacokinetics (PK) and pharmacodynamics of esomeprazole have been described in only a...
BACKGROUND
Although the demand for esomeprazole is increasing in veterinary medicine, the pharmacokinetics (PK) and pharmacodynamics of esomeprazole have been described in only a few studies.
OBJECTIVE
To determine the PK of 0.5 and 1 mg/kg esomeprazole administered IV q12h and to investigate its effects on intragastric pH in healthy dogs.
ANIMALS
Six adult Beagles.
METHODS
Open-label, randomized, and crossover design. The dogs received 0.5 or 1 mg/kg esomeprazole IV q12h for 48 hours. Plasma concentrations of esomeprazole were measured by high-performance liquid chromatography-tandem mass spectrometry. Intragastric pH was determined using the Bravo pH monitoring system and recorded as mean percentage time (MPT) for which pH was ≥3 and ≥4 for 24 hours in each group.
RESULTS
The peak plasma concentration and area under the curve from the time of dosing to the last measurable concentration in the 1 mg/kg group were higher than those in the 0.5 mg/kg group. However, when the dosage normalized, intergroup differences were not significant. The MPTs for which intragastric pH was ≥3 and ≥4 for 48 hours were 88% ± 7% and 81% ± 9% for the 0.5 mg/kg group and 90% ± 9% and 85% ± 11% for the 1 mg/kg group, respectively, with no significant intergroup differences.
CONCLUSIONS AND CLINICAL IMPORTANCE
The pharmacokinetic parameters and acid suppressant effect for 0.5 and 1 mg/kg esomeprazole were not significantly different. Furthermore, the efficacy of esomeprazole 0.5 mg/kg IV q12h was sufficient to increase intragastric pH in Beagles.
Topics: Animals; Anti-Ulcer Agents; Area Under Curve; Chromatography, High Pressure Liquid; Cross-Over Studies; Dogs; Dose-Response Relationship, Drug; Esomeprazole; Gastric Acid; Gastric Acidity Determination; Hydrogen-Ion Concentration; Injections, Intravenous; Random Allocation
PubMed: 30548689
DOI: 10.1111/jvim.15383 -
Journal of Veterinary Internal Medicine Jan 2021Omeprazole preparations vary in bioavailability in horses.
BACKGROUND
Omeprazole preparations vary in bioavailability in horses.
HYPOTHESIS/OBJECTIVES
To characterize the pharmacokinetics and pharmacodynamics of an existing enteric-coated oral omeprazole paste (REF) and a novel, in-feed, enteric-coated dry granule preparation (NOV).
ANIMALS
Twelve Standardbred/Thoroughbred mares free from clinical disease.
METHODS
A prospective, blinded randomized interventional study was trial, conducted in 3 parts: (a) bioavailability study, (b) dose titration study, and (c) comparative clinical pharmacodynamic study, each using a blocked crossover design.
RESULTS
Consistent with the larger dose administered, Cmax (median, 1032 ng/mL; range, 576-1766) and AUC0-24 (median, 63.9 μg/mL*min; range, 42.4-152.4) were greater after single oral administration of NOV than REF (282.7 ng/mL; range, 94.8-390.2, and 319 23.8 μg/mL*min; range, 8.2-42.3, respectively; both P = .004). No differences were observed between products for absolute oral bioavailability (NOV 55% range, 15-88; REF 17% range, 10-77; P = .25). Treatment with both preparations was associated with reduced gastric squamous ulcer scores and increased pH of gastric fluid. Bioequivalence was demonstrated for pharmacodynamic measures with the exception of % time pH <4, despite differences in dose rate and subsequent plasma omeprazole concentrations.
CONCLUSIONS AND CLINICAL IMPORTANCE
The findings of this study indicate that the NOV product would be a suitable alternative to the reference product, and confirm that plasma concentrations of omeprazole and omeprazole dose do not predict drug pharmacodynamics in horses.
Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Cross-Over Studies; Female; Horse Diseases; Horses; Omeprazole; Prospective Studies; Stomach Ulcer
PubMed: 33340169
DOI: 10.1111/jvim.15971 -
Alimentary Pharmacology & Therapeutics Oct 1999The selection of agents to treat patients with acid-related gastrointestinal diseases requires knowledge of their efficacy, tolerability, and ease of dosing among... (Review)
Review
The selection of agents to treat patients with acid-related gastrointestinal diseases requires knowledge of their efficacy, tolerability, and ease of dosing among individuals with differing disease severities and other baseline characteristics. The efficacy and favourable benefit-risk profile of rabeprazole, a new proton pump inhibitor, has been demonstrated in controlled clinical trials of patients with gastro-oesophageal reflux disease (GERD), duodenal ulcers, and gastric ulcers. In comparative trials, rabeprazole is at least as effective as omeprazole for the treatment of GERD, duodenal ulcers, and gastric ulcers, and it is superior to histamine2-receptor antagonists for the treatment of GERD and duodenal ulcers. Its once-daily dosing regimen and low potential for interaction with drugs metabolized by the cytochrome P450 system make it a particularly attractive option for the treatment of acid-related diseases among older individuals. Rabeprazole is likely to be a valuable new addition to its class in treating patients with acid-related gastrointestinal diseases given its efficacy in acid suppression, high healing rates, rapid symptom relief, and convenient dosing.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Enzyme Inhibitors; Gastrointestinal Diseases; Humans; Omeprazole; Rabeprazole; Randomized Controlled Trials as Topic
PubMed: 10555606
DOI: 10.1046/j.1365-2036.1999.00036.x -
Microbiology and Immunology 2000Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to gastric epithelial cells is the initial step of H. pylori...
Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. We have reported that rebamipide and ecabet sodium, mucoprotective antiulcer agents, independently inhibit H. pylori adhesion. However, the antiadhesion activity of each antiulcer agent was incomplete. Experiments were performed to evaluate the combined effect of rebamipide and ecabet sodium on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Twelve clinical isolates of H. pylori were used in this study. We evaluated the effects of rebamipide and ecabet sodium, individually and in combination, on H. pylori adhesion to target cells quantitatively using our previously established enzyme-linked immunosorbent assay. Rebamipide and ecabet sodium each partially inhibited H. pylori adhesion. In contrast, adhesion was almost completely inhibited by pretreating target cells and H. pylori with the combination of rebamipide and ecabet sodium. Our studies suggest that the synergistic antiadhesion activity of rebamipide and ecabet sodium is greater than that of each antiulcer agent alone.
Topics: Abietanes; Alanine; Anti-Ulcer Agents; Bacterial Adhesion; Cell Line; Diterpenes; Drug Synergism; Epithelial Cells; Helicobacter pylori; Humans; Quinolones; Stomach Ulcer
PubMed: 10981828
DOI: 10.1111/j.1348-0421.2000.tb02534.x -
Alimentary Pharmacology & Therapeutics Apr 1998Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro-oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment.
OBJECTIVE
To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects.
METHODS
Intragastric 24-h pH monitoring was performed in 32 healthy subjects in a randomized, double-blind, four-way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days.
RESULTS
Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple-dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple-dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post-regimen serum gastrin values increased by 50-130% from pre-study mean values but remained within normal range and returned to pre-study values 7-14 days post-dosing.
CONCLUSIONS
Multiple-dose regimens of lansoprazole (> or =30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Gastric Acid; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Omeprazole; Peptic Ulcer
PubMed: 9690720
DOI: 10.1046/j.1365-2036.1998.00306.x