RÉSUMÉ
BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.
Sujet(s)
Antibactériens , Association de médicaments , Infections à Helicobacter , Helicobacter pylori , Humains , Infections à Helicobacter/traitement médicamenteux , Infections à Helicobacter/microbiologie , Helicobacter pylori/effets des médicaments et des substances chimiques , Helicobacter pylori/génétique , Mâle , Femelle , Adulte d'âge moyen , Antibactériens/usage thérapeutique , Antibactériens/administration et posologie , République de Corée , Adulte , Sujet âgé , Résultat thérapeutique , Résistance bactérienne aux médicaments , Amoxicilline/usage thérapeutique , Amoxicilline/administration et posologie , Clarithromycine/usage thérapeutique , Métronidazole/usage thérapeutique , Pantoprazole/usage thérapeutique , Génotype , Jeune adulteRÉSUMÉ
Importance: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions. Objective: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs. Design, Setting, and Participants: This cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023. Main Outcomes and Measures: The main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients. Results: Considering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32). Conclusions and Relevance: This cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.
Sujet(s)
Interactions médicamenteuses , Inhibiteurs de la pompe à protons , Humains , Études transversales , Rabéprazole/pharmacologie , Lansoprazole , Oméprazole , Ésoméprazole , PantoprazoleRÉSUMÉ
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Sujet(s)
Pantoprazole , Animaux , Pantoprazole/pharmacocinétique , Pantoprazole/administration et posologie , Ovis , Femelle , Injections sous-cutanées , Concentration en ions d'hydrogène , Inhibiteurs de la pompe à protons/pharmacocinétique , Inhibiteurs de la pompe à protons/administration et posologie , Inhibiteurs de la pompe à protons/pharmacologie , Abomasum/effets des médicaments et des substances chimiques , Administration par voie intraveineuse , Études croisées , Injections veineusesRÉSUMÉ
FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases. The selected drugs were prepared for molecular docking, and the crystal structure of FOXM1 was pre-processed for docking simulations. In vitro studies included MTT assays to assess cytotoxicity, and Western blot analysis to evaluate protein expression levels. Our study identified Pantoprazole and Rabeprazole as potential FOXM1 inhibitors through in silico screening and molecular docking. Molecular dynamics simulations confirmed stable interactions of these drugs with FOXM1. In vitro experiments showed both Pantoprazole and Rabeprazole exhibited strong FOXM1 inhibition at effective concentrations and that showed inhibition of cell proliferation. Rabeprazole showed the inhibitor activity at 10 µM in BT-20 and MCF-7 cell lines. Pantoprazole exhibited FOXM1 inhibition at 30 µM and in BT-20 cells and at 70 µM in MCF-7 cells, respectively. Our current study provides the first evidence that Rabeprazole and Pantoprazole can bind to FOXM1 and inhibit its activity and downstream signaling, including eEF2K and pEF2, in breast cancer cells. These findings indicate that rabeprazole and pantoprazole inhibit FOXM1 and breast cancer cell proliferation, and they can be used for FOXM1-targeted therapy in breast or other cancers driven by FOXM1.
Sujet(s)
Tumeurs du sein , Prolifération cellulaire , Repositionnement des médicaments , Protéine M1 à motif en tête de fourche , Simulation de docking moléculaire , Rabéprazole , Humains , Protéine M1 à motif en tête de fourche/antagonistes et inhibiteurs , Protéine M1 à motif en tête de fourche/métabolisme , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Femelle , Rabéprazole/pharmacologie , Cellules MCF-7 , Prolifération cellulaire/effets des médicaments et des substances chimiques , Simulation de dynamique moléculaire , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Pantoprazole/pharmacologie , Lignée cellulaire tumorale , Pyridines , ThiophènesRÉSUMÉ
BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).
Sujet(s)
Maladie grave , Pantoprazole , Inhibiteurs de la pompe à protons , Ventilation artificielle , Humains , Pantoprazole/usage thérapeutique , Pantoprazole/effets indésirables , Pantoprazole/administration et posologie , Ventilation artificielle/effets indésirables , Mâle , Adulte d'âge moyen , Femelle , Inhibiteurs de la pompe à protons/usage thérapeutique , Inhibiteurs de la pompe à protons/effets indésirables , Inhibiteurs de la pompe à protons/administration et posologie , Sujet âgé , Hémorragie gastro-intestinale/prévention et contrôle , (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles/usage thérapeutique , (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles/effets indésirables , (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles/administration et posologie , Ulcère peptique/prévention et contrôle , Unités de soins intensifs , Pneumopathie infectieuse sous ventilation assistée/prévention et contrôle , Méthode en double aveugle , Stress physiologique , AdulteRÉSUMÉ
Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher Vd compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in Cmax and Tmax between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.
Sujet(s)
Capra , Pantoprazole , Animaux , Mâle , Ovis , Pantoprazole/pharmacocinétique , Pantoprazole/administration et posologie , Injections sous-cutanées/médecine vétérinaire , Injections veineuses/médecine vétérinaire , Inhibiteurs de la pompe à protons/pharmacocinétique , Inhibiteurs de la pompe à protons/administration et posologie , Aire sous la courbe , Biodisponibilité , PériodeRÉSUMÉ
BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.
Sujet(s)
COVID-19 , Humains , COVID-19/prévention et contrôle , COVID-19/épidémiologie , Pantoprazole/usage thérapeutique , SARS-CoV-2 , Unités de soins intensifs/statistiques et données numériques , Pandémies/prévention et contrôle , Femelle , Ventilation artificielle/statistiques et données numériques , Mâle , Protocoles cliniques , Adulte d'âge moyen , Hémorragie gastro-intestinale/prévention et contrôle , Antiulcéreux/usage thérapeutique , Antiulcéreux/administration et posologieRÉSUMÉ
Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.
Sujet(s)
Carcinome hépatocellulaire , Prolifération cellulaire , Glycolyse , Tumeurs du foie , Pantoprazole , Animaux , Carcinome hépatocellulaire/traitement médicamenteux , Carcinome hépatocellulaire/induit chimiquement , Carcinome hépatocellulaire/métabolisme , Glycolyse/effets des médicaments et des substances chimiques , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/induit chimiquement , Tumeurs du foie/métabolisme , Souris , Pantoprazole/pharmacologie , Mâle , Prolifération cellulaire/effets des médicaments et des substances chimiques , Humains , Souris de lignée C57BL , Carcinogenèse/effets des médicaments et des substances chimiques , N-Éthyl-N-nitroso-éthanamine/toxicité , Cytokines/métabolisme , Lignée cellulaire tumorale , Alimentation riche en graisse/effets indésirablesRÉSUMÉ
A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the Tmax of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the Cmax was reduced from 6.162µg/mL to 3.244µg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC0-24 of 19.578 µgâ¢hâ¢mL-1) compared with the commercial drug (AUC0-24 of 17.388 µgâ¢hâ¢mL-1) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.
Sujet(s)
Préparations à action retardée , Pantoprazole , Suspensions , Pantoprazole/pharmacocinétique , Pantoprazole/administration et posologie , Animaux , Mâle , Rats , Libération de médicament , Biodisponibilité , Administration par voie orale , Préparation de médicament , Excipients/composition chimique , Rat Sprague-DawleyRÉSUMÉ
This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical applications. The significance of this study originates from the need to understand the pharmacokinetic changes of TOP after PNT administration, which can inform necessary dose adjustments of TOP. To achieve this, nitrogen blue emissive carbon dots (B@NCDs) were produced and employed due to their unique fluorescent properties. When TOP is added to B@NCDs, it exhibits strong native fluorescence at 545 nm without influencing the B@NCDs' fluorescence at 447 nm. Conversely, PNT causes quenching of B@NCDs fluorescence, a property that enables the distinct detection of both drugs. The B@NCDs were fully characterized using different techniques, including ultraviolet-visible spectrophotometry, fluorescence analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM), and FTIR spectroscopy. The proposed method demonstrated excellent linearity, selectivity, and sensitivity, with low detection limits (LOD, S/N = 3); 0.0016 µg mL-1 for TOP and 0.36 µg mL-1 for PNT. Applied to spiked rabbit plasma samples, this method offers a new approach for evaluating the pharmacokinetic interaction between TOP and PNT. It enables the determination of all pharmacokinetic parameters of TOP before and after coadministration with PNT, providing essential insights into whether dose adjustments are necessary. This research not only contributes to the field of drug monitoring and interaction studies but also exemplifies the potential of B@NCDs in complex biological matrices, paving the way for further pharmacological and therapeutic applications.
Sujet(s)
Carbone , Pantoprazole , Boîtes quantiques , Topotécane , Pantoprazole/pharmacocinétique , Pantoprazole/composition chimique , Topotécane/pharmacocinétique , Topotécane/composition chimique , Topotécane/analyse , Carbone/composition chimique , Boîtes quantiques/composition chimique , Spectrométrie de fluorescence/méthodes , Animaux , Limite de détection , Colorants fluorescents/composition chimiqueRÉSUMÉ
Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
Sujet(s)
Amoxicilline , Antibactériens , Clarithromycine , Association de médicaments , Ésoméprazole , Infections à Helicobacter , Helicobacter pylori , Métronidazole , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Amoxicilline/usage thérapeutique , Antibactériens/usage thérapeutique , Clarithromycine/usage thérapeutique , Clarithromycine/administration et posologie , Calendrier d'administration des médicaments , Ésoméprazole/usage thérapeutique , Ésoméprazole/administration et posologie , Infections à Helicobacter/traitement médicamenteux , Helicobacter pylori/effets des médicaments et des substances chimiques , Métronidazole/usage thérapeutique , Pantoprazole/usage thérapeutique , Inhibiteurs de la pompe à protons/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
The proton-pump inhibitor pantoprazole (PPZ) is one of the most consumed pharmaceuticals worldwide. Despite its high usage, reported PPZ concentrations in environmental water samples are comparatively low, which can be explained by the extensive metabolism of PPZ in the human body. Since most previous studies did not consider human PPZ metabolites it can be assumed that the current environmental exposure associated with the application of PPZ is substantially underestimated. In our study, 4'-O-demethyl-PPZ sulfide (M1) was identified as the predominant PPZ metabolite by analyzing urine of a PPZ consumer as well as the influent and effluent of a wastewater treatment plant (WWTP) using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). M1 was found to be ubiquitously present in WWTP effluents (max. concentration: 3 000 ng/L) and surface waters in Germany. On average, the surface water concentrations of M1 were approximately 30 times higher than those of the parent compound PPZ. Laboratory scale experiments demonstrated that activated carbon can considerably adsorb M1 und thus improve its removal during wastewater and drinking water treatment. Laboratory ozonation experiments showed a fast oxidation of M1, accompanied by the formation of several ozonation products. Certain ozonation products (identities confirmed via synthesized reference standards) were also detected in water samples collected after ozonation in a full-scale WWTP. Overall lower signal intensities were observed in the effluents of a sand filter and biologically active granular activated carbon filter, suggesting that the compounds were significantly removed during these post-ozonation treatment stages.
Sujet(s)
Surveillance de l'environnement , Pantoprazole , Eaux usées , Polluants chimiques de l'eau , Appréciation des risques , Eaux usées/composition chimique , Humains , (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles , Chromatographie en phase liquide , Purification de l'eau , Élimination des déchets liquidesRÉSUMÉ
Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.
Sujet(s)
Amoxicilline , Multirésistance bactérienne aux médicaments , Escherichia coli , Fèces , Microbiome gastro-intestinal , Inuline , Pantoprazole , Animaux , Inuline/pharmacologie , Inuline/métabolisme , Souris , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Escherichia coli/effets des médicaments et des substances chimiques , Escherichia coli/génétique , Fèces/microbiologie , Amoxicilline/pharmacologie , Pantoprazole/pharmacologie , bêta-Lactamases/métabolisme , bêta-Lactamases/génétique , Dysbiose/microbiologie , Dysbiose/traitement médicamenteux , Antibactériens/pharmacologie , Infections à Escherichia coli/traitement médicamenteux , Infections à Escherichia coli/microbiologie , Femelle , Prébiotiques/administration et posologieRÉSUMÉ
Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.
Sujet(s)
Apoptose , Inflammation , Transplantation de cellules souches mésenchymateuses , Cellules souches mésenchymateuses , Stress oxydatif , Pantoprazole , Ulcère gastrique , Animaux , Stress oxydatif/effets des médicaments et des substances chimiques , Ulcère gastrique/induit chimiquement , Rats , Apoptose/effets des médicaments et des substances chimiques , Pantoprazole/pharmacologie , Inflammation/métabolisme , Inflammation/traitement médicamenteux , Cellules souches mésenchymateuses/effets des médicaments et des substances chimiques , Cellules souches mésenchymateuses/métabolisme , Mâle , Transplantation de cellules souches mésenchymateuses/méthodes , Rat Wistar , Antiulcéreux/pharmacologie , Antiulcéreux/administration et posologie , Tissu adipeux/effets des médicaments et des substances chimiques , Tissu adipeux/métabolisme , Association thérapeutiqueSujet(s)
Pantoprazole , Inhibiteurs de la pompe à protons , Humains , Pantoprazole/usage thérapeutique , Inhibiteurs de la pompe à protons/usage thérapeutique , Inhibiteurs de la pompe à protons/effets indésirables , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Débit de filtration glomérulaire/effets des médicaments et des substances chimiques , Résultat thérapeutiqueRÉSUMÉ
This technique is employed for the simultaneous quantification of aspirin (ASP) and pantoprazole sodium in both pure powder form and formulations. The high performance liquid chromatography (HPLC) method uses a C-18 column (250 mm × 4.6 mm, 5 µm) with a mobile phase consisting of 0.05 M disodium hydrogen phosphate and methanol in a 40:60% v/v ratio. The flow rate is maintained at 1.0 mL/min. On a layer of silica gel 60F254 with an aluminum backing, the high performance thin layer chromatography (HPTLC) separation was carried out with ethyl acetate and methanol (8: 1.5 v/v) as the mobile phase. With a mean recovery of 100.54% and 99.55% for ASP and PNT, respectively, quantification was accomplished using the HPLC method with UV detection at 286 nm over the concentration range of 0.1-0.6 g/mL for PNT and 0.4-2.4 g/mL for ASP. With a mean recovery of 99.44% and 99.01% for ASP and PNT, respectively, quantification was achieved using the HPTLC method with UV detection at 298 nm over the concentration range of 400-2400 ng/spot for ASP and 100-600 ng/spot for PNT, respectively. The methods can be used for the simultaneous determination of ASP and PNT in pure powder form and formulations as they are simple, accurate and sensitive.
Sujet(s)
Acide acétylsalicylique , Pantoprazole , Pantoprazole/analyse , Pantoprazole/composition chimique , Acide acétylsalicylique/analyse , Chromatographie en phase liquide à haute performance/méthodes , Reproductibilité des résultats , Modèles linéaires , Chromatographie sur couche mince/méthodes , Limite de détection , (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles/analyse , ComprimésRÉSUMÉ
Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.
Sujet(s)
Dyspepsie , Spirulina , Humains , Inhibiteurs de la pompe à protons/effets indésirables , Dyspepsie/traitement médicamenteux , Dyspepsie/prévention et contrôle , Dyspepsie/induit chimiquement , Pantoprazole/usage thérapeutiqueRÉSUMÉ
INTRODUCTION: Proton pump inhibitors (PPIs) constitute a widely utilized pharmaceutical class, frequently associated with notable instances of therapeutic inappropriateness. Such patterns of misuse not only contribute to elevated healthcare expenditure, but may also exacerbate clinical conditions in certain patients. METHODS: A comprehensive analysis was conducted between 2019 and 2023 to assess all prescriptions dispensed using the Anatomical, Therapeutic and Chemical (ATC) classification system, which allowed trends among primary PPIs to be visualized. This was achieved by calculating the defined daily dose (DDD) and then defining the total expenditure incurred on these drugs. RESULTS: With regard to the prescription of PPIs, an upward trend in consumption was observed with a decreasing expenditure, due to the phenomena of drug generics and increased competition between pharmaceutical companies, ranging from 9,512,481.22 in the first six months of 2019 to 8,509,820.80 in the first six months of 2023. From 2019 to 2023, consumption increased by approximately 3 million DDDs for a total ranging from 18,483,167.59 DDDs to 21,480,871.00 DDDs. Pantoprazole and esomeprazole, the most expensive drugs compared to omeprazole, rabeprazole and lansoprazole, accounted for 61.4% of therapies in the first six months of 2023, up from 2019, where these two drugs were prescribed 54.9%. CONCLUSION: Within this analysis, we provide an illustrative representation of the prescribing trends for PPIs within a European context. Omeprazole, rabeprazole and lansoprazole appear to be the cheapest drugs compared to pantoprazole and esomeprazole. However, the results show that the most widely used PPIs, despite their therapeutic equivalence, are precisely the high-cost ones, thus generating higher expenditure for central governments.
Sujet(s)
Dépenses de santé , Lansoprazole , Pantoprazole , Inhibiteurs de la pompe à protons , Inhibiteurs de la pompe à protons/économie , Inhibiteurs de la pompe à protons/usage thérapeutique , Humains , Lansoprazole/économie , Lansoprazole/administration et posologie , Dépenses de santé/tendances , Dépenses de santé/statistiques et données numériques , Oméprazole/économie , Oméprazole/usage thérapeutique , Ésoméprazole/économie , Rabéprazole/économie , Rabéprazole/administration et posologie , Coûts des médicaments/tendances , Coûts des médicaments/statistiques et données numériques , Médicaments génériques/économie , Utilisation médicament/tendances , Utilisation médicament/statistiques et données numériquesRÉSUMÉ
BACKGROUND: Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. AIMS: This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy. METHODS: This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated. RESULTS: 11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone. CONCLUSIONS: For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.