Rabeprazole was previously defined as a small-molecule fusion inhibitor that binds the conserved hydrophobic HR1 groove of the SARS-CoV-2 spike and blocks six-helix bundle assembly. Here, we expand its antiviral spectrum and demonstrate potent activity against Nipah virus pseudotype, HCoV-229E, and RSV. Using SPR, pseudovirus neutralization, docking, and 100-ns MD simulations, we validated binding of Rabeprazole to the HR1 domains of NiV F glycoprotein and HCoV-229E spike, with a conserved fusion-inhibitory mechanism. Systematic structure-activity relationship (SAR) profiling among clinically approved PPIs revealed that Ilaprazole and Lansoprazole exhibited stronger anti-NiV potency than Rabeprazole, while Rabeprazole sulfide showed enhanced antiviral activity relative to the parent compound. Rabeprazole also inhibited live RSV and HCoV-229E infection in a dose-dependent manner. Collectively, these findings establish the HR1 groove as a druggable pan-viral target and validate benzimidazole-based PPIs as a versatile scaffold for developing orally available, broad-spectrum antivirals against phylogenetically distinct enveloped viruses that rely on class I fusion machinery.

This research presents the development of a novel pH-sensitive PEG (HEMA-co-AA) graft copolymer hydrogel designed to provide controlled and protective delivery of acid-labile drugs, specifically Rabeprazole sodium. The hydrogel was synthesized using polyethylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA), acrylic acid (AA), with N,N'-methylene bisacrylamide (MBA) as a cross-linker and potassium persulfate (KPS) as an initiator. The hydrogel's structural integrity and formation were confirmed through Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling studies. It is noteworthy that the hydrogel exhibits a different pH-dependent swelling behaviour, which expands under alkaline conditions and maintains its compact structure under acidic conditions. The content of acrylic acid contributed to the high-water retention and the swelling profile indicated that the product was suitable for the specific release of the drug at the site. The in-vitro release of rabeprazole sodium at acidic pH is very low, thus protecting rabeprazole sodium from premature degradation in the stomach; however, controlled release of rabeprazole sodium was achieved at intestinal pH via a non-Fickian diffusion mechanism (Korsmeyer-Peppas n = 0.40-0.62, Higuchi R[2] = 0.991-0.996) over 12 h. Moreover, in-vivo acute toxicity studies indicated that the hydrogel is highly biocompatible, suggesting it is safe for use in future therapeutic applications. Overall, the PEG (HEMA-co-AA) hydrogel represents a versatile vehicle for the controlled and local administration of acid-labile pharmaceuticals, thereby promoting increased therapeutic efficacy.

The causal relationship between proton pump inhibitor (PPI) use and bone health outcomes remains uncertain. This study employs a Mendelian randomization (MR) approach to investigate the potential causal association between PPI use and the risk of osteoporosis and fractures. We selected 4 representative PPIs, including omeprazole, esomeprazole, lansoprazole, and rabeprazole, for our study. Bone health outcomes were evaluated through femoral neck bone mineral density (BMD), lumbar spine BMD, and the prevalence of osteoporosis and fracture across various anatomical sites, including the upper arm and shoulder, wrist and hand, lumbar spine and pelvis, femur, and lower leg and ankle. To evaluate PPI exposure and bone health outcomes, we utilized summary statistics derived from genome-wide association studies conducted in European ancestry populations. Primary causal estimates were derived using the inverse-variance weighting (IVW) approach, supplemented by MR-Egger, weighted median, and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods. To strengthen the robustness of our findings, we conducted sensitivity analyses encompassing assessments of heterogeneity, horizontal pleiotropy, and leave-one-out analyses. Lansoprazole demonstrated a significant positive causal effect on femoral neck BMD (IVW: β = 0.137, 95% confidence interval: 0.063-0.210, P = 2.73E-04), whereas no statistically significant effects were observed for lansoprazole on lumbar spine BMD, osteoporosis, or fracture risk. Esomeprazole showed a marginal causal association with an elevated risk of femur fracture (IVW: odds ratio = 1.049, 95% confidence interval: 1.004-1.096, P = .031); however, this association lost statistical significance following Bonferroni correction. Its effects on BMD, osteoporosis, and fractures at other anatomical sites remained nonsignificant. No causal associations with BMD, osteoporosis, or fracture risk were identified for either omeprazole or rabeprazole. Sensitivity analyses further reinforced the robustness and reliability of these findings. This MR analysis found no compelling evidence to support a causal association between PPI use and the risk of osteoporosis or fractures.

Toxoplasmosis is a major health concern with serious consequences in immunocompromised patients and pregnant women. The currently available anti-Toxoplasma therapies have significant limitations including toxicity and emerging resistance. Therefore, there is an urgent need for safe and effective alternative drugs. Repurposing of proton pump inhibitors (PPI) represents a promising strategy because of their reported antiparasitic activities. This study aimed to evaluate the potential therapeutic effect of rabeprazole sodium, a PPI, in a murine model of acute toxoplasmosis in comparison with trimethoprim-sulfamethoxazole (TMP-SMZ). The employed mice were allocated into five groups. Uninfected control, Infected untreated, Infected DMSO-treated, Infected TMP-SMZ-treated, and Infected rabeprazole-treated. Two regimens of rabeprazole were applied; seven-day and ten-day regimens. The efficacy of drugs was assessed through various parameters: parasite load in peritoneal fluid and tissue impression smears, tachyzoite viability rate, scanning and transmission electron microscopy, histopathological and immunohistochemical studies and assay of cytoplasmic and apicoplast triose phosphate isomerase (TPI) enzyme activity. The ten-day regimen of rabeprazole elicited a statistically significant decrease in parasite count in peritoneal fluid, liver and spleen impressions with reductions of 92.16%, 93.83% and 90.91%, respectively. Additionally, tachyzoite viability and TPI activity were significantly affected, and numerous ultrastructural deformities were captured. Favorably, it has obviously ameliorated the tissue pathology through anti-apoptotic impacts and anti-inflammatory properties. To our knowledge, this is the first in vivo study to repurpose rabeprazole against acute toxoplasmosis. In this context, rabeprazole demonstrated superior efficacy to TMP-SMZ enforcing its potential as a promising safe, alternative therapeutic regimen for toxoplasmosis.

Older adults with heart failure (HF) are at high risk of potentially inappropriate medications (PIMs) during hospital discharge, yet real-world data from Asian populations remain limited. This study aimed to investigate the prevalence, spectrum and predictors of PIMs at discharge among older patients with HF in Eastern China. This retrospective cross-sectional study enrolled 468 patients aged ≥ 65 years with chronic HF hospitalized between 2022 and 2024. PIMs were identified according to 2023 American Geriatrics Society Beers Criteria. The primary outcome was PIM prevalence, and predictors were analyzed using multivariable logistic regression. PIMs are highly prevalent in older patients with HF at discharge. Polypharmacy, atrial fibrillation (AF) and renal impairment are the main risk factors. Targeted medication reconciliation and electronic medical record-based alerts are needed to reduce preventable drug-related harm. The overall prevalence of PIMs at discharge was 87.4% (409/468), with a mean of 2.4 ± 1.8 PIM instances per patient. Three independent predictors were identified: discharge medication count ≥ 7 (aOR = 3.45, 95% confidence interval (CI): 2.10-5.66), AF (adjusted odds ratio [aOR] = 2.98, 95% CI: 1.89-4.68), and eGFR < 45 mL/min/1.73m2 (aOR = 1.74, 95% CI : 1.05-2.88). A synergistic interaction between AF and polypharmacy further elevated PIM risk. Common PIMs included furosemide, rabeprazole and rivaroxaban.

OJT007 is a novel drug class with potent antiproliferative effects against Leishmania Major. The drug is amphoteric with a key basic amine pKa of 5.8 and acid liable. Pre-systemic metabolism in gastric acidic compartment is suspected as a major factor for its low oral bioavailability. To validate this biopharmaceutical assumption, we evaluated in vitro stability and solubility profiles of OJT007 in various buffers (pH 1.2-7). We further conducted a pharmacokinetic drug-drug interaction study where OJT007 was orally administered alone or following pre-treatment of rabeprazole, a prescription proton pump inhibitor that reduces stomach acid using rat as an animal model. The in vitro degradation of OJT007 was rapid at pH 1.2-3 with less than 50% drug remaining within 30 min. Solubility of OJT007 was also pH-dependent with a solubility of 31.3 µg/mL at pH 1.2 and practically insoluble at pH above 6. Interestingly in the in vivo studies, there were approximately 40% reduction in the mean maximum plasma drug concentration (Cmax) and the mean area under the plasma concentration versus time curve (AUC0-∞) in the rat group pre-treated with rabeprazole as compared to OJT007 alone. As opposed to our initially hypothesized, OJT007 degradation under gastric acidic pH was not a major factor controlling oral bioavailability of the drug. Instead, low solubility at a higher pH might have contributed to the observed low bioavailability. The findings illustrate that optimizing oral bioavailability for OJT007 requires formulation strategies that simultaneously address solubility at intestinal pH and stability in the stomach.

Proton pump inhibitors (PPIs) are among the most widely prescribed medications for gastric acid-related disorders. However, their effect on the gut microbiota remains incompletely understood, despite emerging evidence suggesting potential long-term alterations in microbial composition and reductions in beneficial taxa. In this study, Lactobacillus acidophilus, a well-known probiotic species, was used as a representative model organism to investigate the microbiological effects of PPIs. This specific bacterium is linked to immune modulation, vitamin metabolism, and the preservation of the epithelial barrier. The effects of PPIs on L. acidophilus at the structural and functional levels were elucidated by an integrated framework including subtractive genomics, molecular docking, molecular dynamics (MD) simulations, antimicrobial assays, and transcriptional analysis. Using a multi-criteria scoring system, essential, non-redundant, non-human homologous cytoplasmic proteins were ranked and mapped to important pathways such as ATP synthesis, peptidoglycan biosynthesis, amino-sugar metabolism, nucleotide metabolism, and protein maturation. Molecular docking suggested potential binding of pantoprazole and rabeprazole to targets such as MurA, MurB, MurE, GlmS, NadE, AtpD, Def, and PyrH proteins. MD simulation showed stable protein-PPI complexes with localized flexibility changes near catalytic domains while preserving the global fold. Consistent with in-silico expectations, both pantoprazole and rabeprazole exhibited dose-dependent growth inhibition of L. acidophilus, whereas qRT-PCR revealed transcriptional downregulation of genes involved in cell-wall production, NADH metabolism, and energy generation. Pantoprazole elicited the most uniform transcriptional suppression, whereas rabeprazole had stronger but more varied effects. The present findings provide preliminary insights into potential interactions between PPIs and probiotic bacteria at the molecular and cellular levels. However, the results reflect species-specific responses under in vitro conditions and should be interpreted cautiously, as transcriptional changes do not directly confirm functional inhibition and the concentrations tested may represent upper-range exposure scenarios. Further in vivo and multi-species studies are required to validate this observation and better understand their clinical implications for microbiome stability during PPI therapy.

Advanced in silico tools, such as physiologically based biopharmaceutics models (PBBM) and physiologically based pharmacokinetic models (PBPK), play a pivotal role in model-informed formulation development (MIFD). In the present study, these methodologies were utilized in the development of a novel rabeprazole modified-release (MR) formulation for improved patient compliance by reducing the dosing frequency relative to existing delayed-release (DR) formulation. A MR formulation containing combination of delayed release and pulsatile release components was designed based on the hypothetical dissolution targets. A PBBM was first established using literature-derived clinical data and used to simulate the performance of formulations with varied dissolution profiles. Initial MR formulation prototypes (once a day) were evaluated in pilot-1 bioequivalence (BE) study against reference formulation (twice a day) but results indicated infra bioequivalence outcome. After pilot-1 study, the formulation and the dissolution method were optimized and then model was refined to predict the pilot 1 outcomes. The validated model was then employed to select suitable pilot-2 prototypes and to prospectively predict their BE outcomes under fasted and fed conditions. The predicted BE ratios were in good agreement with the observed pilot-2 study results. Therefore, the same model was used to make prospective predictions with increased subjects to understand the in vivo performance of pivotal test formulation and lead to the successful bioequivalence outcome, product commercialization, ultimately aiding in increased patient compliance. This work highlights the value of a model-informed strategy in accelerating formulation optimization, reducing development timelines and costs, and strengthening decision-making within pharmaceutical development programs.