Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαβ+ CD4+ IL-17A+ and TCRαβ+ CD8+ IL-17A+ T cells and increased frequency of TCRαβ+ CD4+ CD25+ FoxP3+ Treg, and TCRαβ+ CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.

Levosulpiride and omeprazole are co-prescribed for gastrointestinal disorders associated with depression and anxiety. Objective of the study was to develop a sensitive, robust and simple method for simultaneous analysis of levosulpiride and omeprazole in human plasma and applicability of the method in determination of pharmacokinetics drug-drug interaction. In the presented study, a reversed-phase HPLC-UV method was developed for the simultaneous determination of levosulpiride and omeprazole using pantoprazole as the internal standard. Experimental conditions were optimized and the developed method was validated as per standard guidelines (USP and ICH). Furthermore, the developed method was applied for evaluation of pharmacokinetics drug-drug interaction between levosulpiride (50 mg) and omeprazole (40 mg) in healthy human volunteers. Sharpsil C8 column (4.6 × 250 mm, 5 μm), Ultisil C8 column (4.6 mm × 150 mm, 5 μm) and Agilent C18 column (4.6 × 250 mm, 5 μm) were evaluated as stationary phase. The best resolution was achieved with Agilent C18 (4.6 x 250 mm, 5 μm) column and was selected for further study. The mobile phase consisted of a mixture of acetonitrile and phosphate buffer (pH 7.2) in 60:40 by volume, and was pumped at a flow rate of 1 mL/min. Detector wavelength was set at 280 nm. Levosulpiride and omeprazole were extracted from human plasma with ethyl acetate and dichloromethane (4:1, v/v). The calibration curves for both levosulpiride (5-150 ng/mL) and omeprazole (10-1500 ng/mL) were linear. The lower limit of quantification and limit of detection for levosulpiride were 5 and 2 ng/mL, while for omeprazole these were 10 and 3 ng/mL, respectively. Pharmacokinetics analysis showed that co-administration of omeprazole increased the AUC and Cmax of levosulpiride, while the clearance was reduced. Both the changes were insignificant. Similarly, no significant change in the pharmacokinetic parameters of omeprazole was observed with co-administration of levosulpiride.

OBJECTIVE: This study addresses a critical need in pediatric pharmacotherapy by focusing on the development of an enteric formulation of omeprazole for pediatric use. Omeprazole, a widely used proton pump inhibitor, is essential for treating various gastrointestinal disorders in children. The main objective is to design a compounding formula that can be prepared in hospital pharmacy services without the need for industrial equipment, which is often unavailable in these settings.
METHODS: The research applied different galenic strategies to overcome the challenges of omeprazole\'s instability in acidic environments and its complex pharmacokinetic and physicochemical properties. The experiments were conducted sequentially, employing salting out, ionic gelation, and matrix granulation strategies. Based on the results obtained, the control conditions and parameters for the various trials were established.
RESULTS: Among the techniques used, wet granulation proved to be the most promising, achieving a gastro-resistance level of 44%. In contrast, the ionic gelation and salting-out techniques did not yield satisfactory results.
CONCLUSIONS: The findings of this study underscore the need to adopt alternative formulation strategies to ensure the stability of omeprazole. This goal requires a multidisciplinary approach and continuous effort to design omeprazole formulations that meet quality standards and appropriate gastro-resistance requirements.

OBJECTIVE: Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection.
METHODS: A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups.
RESULTS: In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups.
CONCLUSIONS: The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.

OBJECTIVE: Numerous clinical concerns have been expressed regarding the potential worsening of cyclin-dependent kinase 4/6 inhibitor effects in breast cancer patients because of co-administration of proton pump inhibitors. Hence, this study evaluated the effects of proton pump inhibitors on the pharmacokinetics of palbociclib and ribociclib in terms of  cytochrome P450 (CYP) 3A4 and P-glycoprotein involvement.
METHODS: The effects of omeprazole and rabeprazole on drug metabolism and efflux of these drugs were investigated using molecular docking, metabolic stability assay in rat liver microsomes, human recombinant CYP3A4 (rCYP3A4) enzymes, and Caco-2 cell monolayers, and in vivo pharmacokinetics with omeprazole and rabeprazole in (5 and 10 mg/kg) 30 min and 7 days before orally dosing palbociclib and ribociclib (10 mg/kg).
RESULTS: Omeprazole and rabeprazole inhibited CYP3A4 enzyme activity in rCYP3A4 baculosomes with a 50-60% inhibition at 30 μM. Additionally, both omeprazole and rabeprazole (10 µm) significantly reduced the P-glycoprotein-mediated drug efflux of palbociclib and ribociclib. The 7-day pretreatment of omeprazole at a dose of 10 mg/kg resulted in 24% and 26% reductions in palbociclib\'s mean maximum plasma concentration) Cmax and area under the plasma concentration-time curve (AUC0-24 h), respectively. Palbociclib\'s pharmacokinetics were not significantly altered by the pretreatment with rabeprazole; however, ribociclib pharmacokinetics exhibited an 83.94% increase in AUC0-24 h.
CONCLUSIONS: The findings indicate that long-term treatment with therapeutic doses of both omeprazole and rabeprazole can alter the pharmacokinetics of palbociclib and ribociclib. The co-administration of rabeprazole may alter the pharmacokinetics of palbociclib and ribociclib via CYP enzyme and P-glycoprotein inhibition.

BACKGROUND: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis.
METHODS: We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs).
RESULTS: Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes.
CONCLUSIONS: Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

UNASSIGNED: 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.
UNASSIGNED: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

BACKGROUND: Insulin autoantibody syndrome (IAS), or Hirata disease, is caused by high concentrations of insulin autoantibodies, which result in spontaneous, mainly post-prandial, hypoglycemic episodes. We report a case of a previously healthy 67-year-old man presenting with recurrent fasting hypoglycemia culminating in a diagnosis of insulin autoimmune syndrome linked to omeprazole and probably spices, namely, coriander, and ginger.
METHODS: A previously healthy 67-year-old Sinhalese man presented with recurrent syncopal attacks for 3 months, which were found to be hypoglycemic episodes. He experienced mainly fasting hypoglycemic attacks, at a frequency gradually increasing to daily attacks. His cardiovascular, respiratory, abdominal, and neurologic examinations were normal. He was found to have insulin levels > 6000 mU/L and a post-polyethylene glycol insulin recovery of less than 9.5%. Contrast-enhanced computed tomography of the pancreas was normal. The diagnosis of insulin autoantibody syndrome was confirmed by testing for the insulin autoantibody level, yielding a level of > 300 U/mL. With regard to a possible trigger, he had a history of omeprazole intake for 2 weeks, 4 weeks prior to the onset of symptoms. He also consumed an herbal supplement containing coriander and ginger extracts daily for a period of 1 year, approximately 2 years prior to the onset of hypoglycemic attacks. He was commenced on prednisolone 30 mg daily, and hypoglycemic episodes responded dramatically, and thus he was tapered off corticosteroids.
CONCLUSIONS: Omeprazole-induced insulin autoantibody syndrome is likely in this patient; however, the known hypoglycemic effects of coriander and ginger make it worthwhile to consider a possible association with insulin autoantibody syndrome. In addition, this case report highlights the need to consider insulin autoantibody syndrome even in patients presenting with fasting hypoglycemic attacks.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed.
OBJECTIVE: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment.
METHODS: Fifty-one dogs with mast cell tumors (MCTs).
METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor.
RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups.
CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.