Gastric acid is essential for digestion, host defense, and maintenance of gastrointestinal homeostasis; however, its excessive or inappropriate secretion contributes to the development and progression of several acid-related disorders. Proton pump inhibitors (PPIs) have remained the cornerstone of acid-suppressive therapies for more than four decades owing to their potent blockade of gastric H[+]/K[+]-ATPases. This review provides a comprehensive overview of the pharmacological properties, clinical applications, and current limitations of the most widely used PPIs, including omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. Particular emphasis is placed on their role in the management of Helicobacter pylori infection, a strong risk factor for the development of severe gastric diseases and one of the most clinically important indications for PPI-based antibiotic therapy. Beyond elevating intragastric pH to enhance antibiotic stability and efficacy, accumulating evidence indicates that PPIs exert direct antibacterial activity against H. pylori and may act synergistically with selected antibiotics. The review also discusses emerging evidence for interindividual variability in PPI metabolism, drug-drug interactions, and concerns regarding long-term adverse effects of the current treatments. Finally, it highlights potassium-competitive acid blockers (P-CABs), a newer class of acid-suppressive agents that provide sustained acid inhibition and represent a promising alternative to PPI-based regimens for H. pylori eradication.

Rabeprazole is a highly variable drug for which demonstration of bioequivalence is often challenging, and CYP2C19 genotype and sex have been suggested as potential contributors to pharmacokinetic variability. We evaluated the pharmacokinetics, bioequivalence (BE), and tolerability of a generic rabeprazole formulation compared with the reference product in healthy Korean participants using an open-label, randomized, single-dose, two-sequence, four-period replicated crossover design with a scaled average BE (SABE) approach. Exploratory subgroup analyses according to CYP2C19 genotype and sex were also performed. Fifty-two participants received single 20 mg doses under fasting conditions, and 46 completed the trial. BE was evaluated using SABE and conventional average BE (ABE), with subgroup analyses by genotype and sex. Geometric mean ratios (GMRs) of the test to reference formulations were within the BE acceptance range under ABE and SABE approaches. The reference formulation showed high intra-CV in maximum plasma concentration (Cmax; 67.9%), consistent with the classification of rabeprazole as a highly variable drug. These results demonstrated bioequivalence between the test and reference formulations under both conventional average bioequivalence and scaled bioequivalence approaches.

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.