Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

• MeSH
• antibakteriální látky terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   epidemiologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• nádory žaludku * prevence a kontrola   epidemiologie   mikrobiologie   MeSH
• omeprazol * terapeutické užití   aplikace a dávkování   MeSH
• organokovové sloučeniny terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• tetracyklin terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Čína epidemiologie   MeSH
• Názvy látek
• antibakteriální látky MeSH
• metronidazol MeSH
• omeprazol * MeSH
• organokovové sloučeniny MeSH
• tetracyklin MeSH

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.

• Klíčová slova
• bioequivalence study, dissolution, enteric coating, industrial development, omeprazole, pellets, stability study,
• MeSH
• klinické křížové studie MeSH
• lidé MeSH
• omeprazol * chemie   MeSH
• terapeutická ekvivalence MeSH
• tobolky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• omeprazol * MeSH
• tobolky MeSH

Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel dasatinib anhydrate containing formulation was to demonstrate improved absorption and lower pharmacokinetic variability compared to dasatinib monohydrate. In a bioavailability study comparing formulations containing 110.6 mg and 140 mg of dasatinib as anhydrate and monohydrate, respectively, both Cmax and AUC of dasatinib were within standard 80.00-125.00% range, while the intra- and inter-subject variability for AUC0-inf after the test product was approximately 3-fold and 1.5-fold less than after the reference, respectively.In a drug-drug interaction study, omeprazole 40 mg reduced the mean AUC0-inf of dasatinib by 19%, when the test was ingested 2 h before the 5th omeprazole dose. This decrease of exposure is clinically irrelevant and substantially less than after the reference. Co-prescription analysis supports the importance of pH-dependent solubility of dasatinib, as >21% of patients were treated concomitantly with a PPI and dasatinib despite warnings against this co-medication in the SmPC.The novel dasatinib anhydrate containing formulation demonstrated improved absorption and less pharmacokinetic variability compared to dasatinib monohydrate product, which may translate into improved clinical outcomes, although this needs to be proven by an appropriate trial.

• MeSH
• aplikace orální MeSH
• biologická dostupnost MeSH
• dasatinib MeSH
• klinické křížové studie MeSH
• lidé MeSH
• omeprazol * farmakokinetika   MeSH
• plocha pod křivkou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dasatinib MeSH
• omeprazol * MeSH

ACT-1014-6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto-inflammatory diseases. The in vitro inhibition potential of ACT-1014-6470 on cytochrome P450 isozymes (CYPs) and its effect on the pharmacokinetics (PK) of the CYP2C19 and CYP3A4 substrates omeprazole and midazolam, respectively, in humans were assessed. In vitro assays were conducted with isoform-specific substrates in human liver microsomes. In an open-label, two-period, fixed-sequence cocktail study, single doses of 20 mg omeprazole and 2 mg midazolam were administered concomitantly to 20 healthy male subjects alone (treatment A) and after a single dose of 100 mg ACT-1014-6470 (treatment B) under fed conditions. Safety and PK assessments were performed. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of noncompartmental PK parameters of treatment B versus treatment A were calculated. In vitro, no time-dependent inhibition was observed and the lowest inhibition constant of 4.3 μM ACT-1014-6470 was recorded for CYP2C19. In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5-2.5) for maximum plasma concentration (Cmax ) and 1.9 (1.5-2.3) for area under the plasma concentration-time curve from 0 to 12 h (AUC0-12 h ). Midazolam PK showed GMRs (90% CI) of 1.1 (1.1-1.2) for Cmax and 1.5 (1.4-1.6) for AUC0-24 h . All treatments were well-tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT-1014-6470 reflected a weak inhibition of CYP2C19 and CYP3A4.

• MeSH
• cytochrom P-450 CYP3A * MeSH
• cytochrom P450 CYP2C19 MeSH
• faktor Va * MeSH
• lékové interakce MeSH
• lidé MeSH
• midazolam farmakokinetika   MeSH
• omeprazol farmakokinetika   MeSH
• systém (enzymů) cytochromů P-450 MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ACT-1014-6470 MeSH Prohlížeč
• cytochrom P-450 CYP3A * MeSH
• cytochrom P450 CYP2C19 MeSH
• faktor Va * MeSH
• midazolam MeSH
• omeprazol MeSH
• systém (enzymů) cytochromů P-450 MeSH

BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.

• Klíčová slova
• GERD or GORD, acidity (esophageal), compliance/adherence, functional GI diseases,
• MeSH
• dvojitá slepá metoda MeSH
• esomeprazol * terapeutické užití   MeSH
• gastroezofageální reflux * farmakoterapie   diagnóza   MeSH
• inhibitory protonové pumpy terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pyróza farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine MeSH Prohlížeč
• esomeprazol * MeSH
• inhibitory protonové pumpy MeSH

OBJECTIVES: To examine the prescribing habits for omeprazole in a veterinary teaching hospital and to evaluate the effect of a clinical audit on omeprazole prescription. MATERIAL AND METHODS: Observational study with retrospective clinical audit followed by a prospective study. The evaluated data about omeprazole prescription included the dose, frequency and indication. These were assessed according to published guidelines. A seminar about the audit and current guidelines on the use of omeprazole was organised for all members of clinical staff. Prospective data collection was conducted after the seminar. A comparison of the collected data before and after the clinical audit was made. RESULTS: A total of 301 dogs were prescribed omeprazole in the veterinary teaching hospital during the study period (including the retrospective and prospective parts). Complete data were acquired from 240 patients. The prescribed frequency of omeprazole was inappropriate in 23 (16.5%) of the prescriptions in the retrospective section but in only five (5.0%) in the prospective study. Inappropriate indications were reported in 12 (8.6%) patients in the retrospective section and in two patients (2.0%) in the prospective study. Overall inappropriate omeprazole prescription was identified in 34 (24.5%) patients in the retrospective part and in seven (6.9%) patients in the prospective part. There was a statistically significant difference between the two groups in frequency, indication and overall prescription of omeprazole. CLINICAL SIGNIFICANCE: This study details the frequency of inappropriate prescription of omeprazole in a veterinary teaching hospital and provides some evidence that dissemination of guidelines based on clinical audit can improve prescribing habits.

• MeSH
• nemocnice fakultní MeSH
• nemocnice veterinární * MeSH
• omeprazol * terapeutické užití   MeSH
• prospektivní studie MeSH
• psi MeSH
• retrospektivní studie MeSH
• zvířata MeSH
• zvyky MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• observační studie veterinární MeSH
• Názvy látek
• omeprazol * MeSH

Proton pump inhibitors, such as omeprazole, pantoprazole and lansoprazole, are an important group of clinically used drugs. Generally, they are considered safe without direct toxicity. Nevertheless, their long-term use can be associated with a higher risk of some serious pathological states (e.g. amnesia and oncological and neurodegenerative states). It is well known that dysregulation of the metabolism of transition metals (especially iron ions) plays a significant role in these pathological states and that the above drugs can form complexes with metal ions. However, to the best of our knowledge, this phenomenon has not yet been described in water systems. Therefore, we studied the interaction between these drugs and transition metal ions in the surrounding water environment (water/DMSO, 99:1, v/v) by absorption spectroscopy. In the presence of Fe(III), a strong redshift was observed, and more importantly, the affinities of the drugs (represented as binding constants) were strong enough, especially in the case of omeprazole, so that the formation of a metallocomplex cannot be excluded during the explanation of their side effects.

• Klíčová slova
• complexation study, drug interactions, iron metal complexes, proton pump inhibitor, transition metals,
• MeSH
• inhibitory protonové pumpy chemie   MeSH
• komplexní sloučeniny chemie   MeSH
• lanzoprazol * chemie   MeSH
• omeprazol chemie   MeSH
• pantoprazol chemie   MeSH
• přechodné kovy chemie   MeSH
• spektrofotometrie * MeSH
• voda chemie   MeSH
• železité sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory protonové pumpy MeSH
• komplexní sloučeniny MeSH
• lanzoprazol * MeSH
• omeprazol MeSH
• pantoprazol MeSH
• přechodné kovy MeSH
• voda MeSH
• železité sloučeniny MeSH

BACKGROUND: The aim of this study was comparison the effectiveness of sequential and standard quadruple therapy on eradication of H. pylori infection. METHODS: This clinical trial study was conducted on 160 patients with dyspepsia or gastroduodenal ulcer. Patients were randomly divided into two groups. Group A (standard regimen) received omeprazole, amoxicillin, clarithromycin and bismuth subcitrate for 2 weeks. Group B (sequential regimen) received omeprazole and amoxicillin in 5 days and omeprazole, tinidazole and levofloxacin in 5 days. After the end of treatment regimens, 20 mg omeprazole was administered twice daily for 3 weeks. H. pylori eradication was assessed 2 months after antibiotic treatment via fecal antigen. RESULTS: Frequency of H. pylori eradication in group A and B was observed in 55 (68.8%) and 63 patients (78.8%), respectively. No significant difference was seen between two groups, regarding H. pylori eradication (p = 0.15). The most common side effects in group A, B were bitterness of mouth (63.8%) and nausea (16.2%), respectively (p H. pylori infection, higher rate of H. pylori eradication was seen in group B than group A. Thus, sequential regimen was a more appropriate regimen with fewer complications.

• Klíčová slova
• H. pylori infection, Sequential therapy, eradication, standard triple-drug therapy,
• MeSH
• amoxicilin aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori MeSH
• infekce vyvolané Helicobacter pylori farmakoterapie   MeSH
• klarithromycin aplikace a dávkování   MeSH
• kombinovaná farmakoterapie MeSH
• levofloxacin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• omeprazol aplikace a dávkování   MeSH
• organokovové sloučeniny aplikace a dávkování   MeSH
• senioři MeSH
• tinidazol aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH
• Názvy látek
• amoxicilin MeSH
• bismuth tripotassium dicitrate MeSH Prohlížeč
• klarithromycin MeSH
• levofloxacin MeSH
• omeprazol MeSH
• organokovové sloučeniny MeSH
• tinidazol MeSH

Data on gastric pH in rats to be used in preclinical models for pH-dependent drug absorption are still limited or contradictory. The aim of this study was to describe gastric pH in rats at fasted state and to evaluate its changes induced by pentagastrin or omeprazole in order to mimic gastric pH at fasted and fed human subjects. Twenty Wistar rats, fasting for 12 h, were randomly assigned into four treatment groups (n=5): control, pre-treated with omeprazole 2 h before pH measurement, pre-treated with omeprazole 12 h before pH measurement, and pre-treated with pentagastrin 20 min before pH measurement. An incision on the stomach wall was made in anesthetized animals, and pH of gastric juice was measured. The observed pH values were significantly different among groups (p=0.0341), with the median (IQR) values of gastric pH of 3.5 (2.7-4.2), 6.7 (4.7-7.0), 5.6 (3.5-6.4) and 2.2 (1.6-3.1) in control, omeprazole 2 h, omeprazole 12 h and pentagastin group, respectively. We recommend using short interval pentagastrin and 2 h omeprazole pre-treatment in fasting animals to model similar gastric pH as is expected in human fasted and fed state pharmacokinetic studies, respectively.

• Klíčová slova
• Gastric pH, Omeprazole, Oral drug absorption, Pentagastrin, Rats,
• MeSH
• inhibitory protonové pumpy * farmakokinetika   MeSH
• koncentrace vodíkových iontů MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely u zvířat MeSH
• náhodné rozdělení MeSH
• omeprazol * farmakokinetika   MeSH
• potkani Wistar MeSH
• žaludeční sliznice * MeSH
• žaludek * chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory protonové pumpy * MeSH
• omeprazol * MeSH

The purpose of this work was to develop a new supergeneric product Meloxicam/Omeprazole. Such a combination brings a benefit in terms of decreasing side effects for the patients using meloxicam. The new combination is composed of a meloxicam powder blend (MPB) and omeprazole gastro-resistant pellets (OAP) in hard gelatin capsules. The main tasks were to select the excipients to keep the functional layer of OAP active and to prove the bioequivalence to the original products of meloxicam tablets together with omeprazole capsules. Although dissolution profiles similar to the original product were obtained, the unexpected results of omeprazole low bioavailability in the fed bioequivalence study (BES I) showed the necessity to investigate the formulation in greater depth. A modified more complex dissolution method was developed in order to understand the release of omeprazole under gastric conditions. This method revealed the degradation of omeprazole in the formulation when exposed to the fed conditions because of the increase in microenvironmental pH in the capsule caused by trisodium citrate, commonly used for improving solubility of meloxicam. This pH increase dissolved the gastro-resistant layer of OAP and caused the chemical degradation. To prevent this effect, a trisodium citrate-free formulation was developed. Reformulated capsules passed the repeated fed bioequivalence study (BES II).

• Klíčová slova
• Bioequivalence study, Biorelevant dissolution, Meloxicam, Omeprazole, Supergeneric product,
• MeSH
• antiflogistika nesteroidní * aplikace a dávkování   chemie   farmakokinetika   MeSH
• citráty chemie   MeSH
• farmaceutická chemie MeSH
• fixní kombinace léků MeSH
• klinické křížové studie MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• meloxikam MeSH
• omeprazol * aplikace a dávkování   chemie   farmakokinetika   MeSH
• pomocné látky chemie   MeSH
• prášky, zásypy, pudry MeSH
• protivředové látky * aplikace a dávkování   chemie   farmakokinetika   MeSH
• terapeutická ekvivalence MeSH
• thiaziny * aplikace a dávkování   chemie   farmakokinetika   MeSH
• thiazoly * aplikace a dávkování   chemie   farmakokinetika   MeSH
• tobolky MeSH
• uvolňování léčiv MeSH
• želatina chemie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• antiflogistika nesteroidní * MeSH
• citráty MeSH
• fixní kombinace léků MeSH
• meloxikam MeSH
• omeprazol * MeSH
• pomocné látky MeSH
• prášky, zásypy, pudry MeSH
• protivředové látky * MeSH
• thiaziny * MeSH
• thiazoly * MeSH
• tobolky MeSH
• trisodium citrate MeSH Prohlížeč
• želatina MeSH