omeprazole

Overview

Omeprazole is a benzimidazole-class proton pump inhibitor (PPI) that irreversibly inhibits the hydrogen-potassium ATPase enzyme system (H⁺/K⁺-ATPase) located on the secretory surface of gastric parietal cells, thereby suppressing gastric acid secretion. It is one of the most widely prescribed medications globally and is indicated for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, Helicobacter pylori eradication (in combination regimens), and other acid-related gastrointestinal disorders across both adult and pediatric populations. Omeprazole is a prodrug that is activated under acidic conditions in the gastric canaliculus, where it forms a covalent disulfide bond with cysteine residues of the proton pump.

From a pharmacokinetic standpoint, omeprazole is predominantly metabolized by cytochrome P450 enzymes in the liver, with cytochrome P450 family 2 subfamily C member 19 (CYP2C19) playing a central role in its primary metabolic clearance. This dependence on CYP2C19 makes omeprazole a clinically relevant substrate for assessing drug-drug interactions, and it is routinely used as a probe compound in pharmacokinetic studies evaluating CYP2C19 inhibition or induction by investigational agents.

Focus of Latest Publications

Recent scientific literature positions omeprazole at the intersection of several diverse research areas, extending well beyond its established role as a gastric acid suppressant.

Antiviral and Drug Repurposing Research: A 2026 study published in Bioorganic Chemistry (PMID: 41691755) used DNA-encoded library screening to identify repurposed drugs capable of targeting the SARS-CoV-2 spike protein heptad repeat 1 (HR1) domain, a region critical for viral membrane fusion. Omeprazole was identified as one of the hits from this screen, alongside rabeprazole-related compound E, alvimopan, and olmesartan, and was subsequently characterized using biophysical assays and cell-cell fusion assays. This finding positions omeprazole as a candidate for further antiviral investigation under the drug repurposing paradigm.

Anticancer and Tubulin Inhibition Research: A machine learning-driven computational study (PMID: 41689974, Bioorganic & Medicinal Chemistry, 2026) applied quantitative structure-activity relationship (QSAR) modeling and molecular dynamics simulations to identify novel tubulin inhibitors for cancer therapy. Omeprazole was among four compounds—alongside podofilox, sulfadoxine, and trimethoprim—that demonstrated stable binding at the colchicine site of tubulin, with favorable binding free energies calculated via MM-GBSA methodology over 200 ns simulations. These results suggest a previously underappreciated potential for omeprazole in oncological drug repurposing.

Anti-parasitic Activity: A 2026 study in Veterinary Medicine and Science (PMID: 42035445) evaluated omeprazole as a novel treatment for giardiasis in cats, based on in vitro evidence that omeprazole inhibits giardial triosephosphate isomerase, a metabolic enzyme essential to the parasite. This anti-giardial mechanism represents a pharmacologically distinct activity from its canonical proton pump inhibition.

Pediatric Formulation Research: A comparative sensory evaluation published in Clinical Drug Investigation (PMID: 41927994) assessed pediatric liquid omeprazole formulations available in the United Kingdom, underscoring the ongoing clinical importance of developing palatable and bioavailable formulations for pediatric GERD and acid-related conditions in children.

Gastric pH Sensing and Diagnostics: Research in Science Advances (PMID: 42102190) used omeprazole as a pharmacological tool to induce controlled pH changes in vivo—shifting gastric pH from approximately 2 to 6 (ΔpH = 4)—to validate a soft robotic ingestible device called SeroTab for real-time gastric molecular sensing. The study also identified 42 Metabolites in the gastric environment following omeprazole administration, illustrating its utility as a physiological probe in diagnostic device development.

Drug-Drug Interaction Studies: A phase 1 clinical study examining the drug interaction potential of lotiglipron (PF-07081532) used omeprazole explicitly as a CYP2C19 substrate probe (PMID: 42053447), reflecting the compound's established role in clinical pharmacology to quantify CYP2C19 modulation by new investigational drugs. Separately, a study on GS-1427, an oral prodrug of an α4β7 integrin inhibitor (PMID: 41854177), reported that omeprazole co-administration reduced exposure to the active metabolite GS-1069518 by approximately 20–40%, highlighting how gastric pH elevation by omeprazole can alter the absorption of pH-sensitive drugs.

Toxicological Characterization: A toxicological study (PMID: 40719247, Drug and Chemical Toxicology, 2026) specifically investigated the safety profile of two omeprazole degradation impurities found in intravenous formulations—omeprazole-sulfone and omeprazole-N-oxide—providing important regulatory and safety data for parenteral omeprazole products.

Lactation Pharmacology: A study on pantoprazole excretion into breast milk (PMID: 42168392) used omeprazole as an internal standard in a validated high-performance liquid chromatography (HPLC) analytical method, reflecting the compound's physicochemical suitability as a reference comparator in PPI bioanalytical workflows.

Key Publications

Jun Rapid discovery of repurposed drugs targeting SARS-CoV-2 spike HR1 by DNA-encoded library screening. (Bioorganic chemistry, 2026, PMID 41691755): "Hits including Rabeprazole-related compound E (Rab RCE), Omeprazole, Alvimopan, and Olmesartan were characterized."
Jun Comparative Sensory Evaluation of Pediatric Liquid Omeprazole Formulations Available in the UK. (Clinical drug investigation, 2026, PMID 41927994): "Omeprazole is a widely prescribed proton pump inhibitor used to treat gastroesophageal reflux disease and other acid-related disorders in children."
May Maternal PPI therapy during lactation: pantoprazole levels in human milk and possible neonatal implications. (European journal of pediatrics, 2026, PMID 42168392): "Pantoprazole was quantified using a validated high-performance liquid chromatography (HPLC) method with omeprazole as the internal standard."
May Electronics-free soft robotic minitablet for on-demand gastric molecular sensing and diagnostics in vivo. (Science advances, 2026, PMID 42102190): "In vivo studies in animal models demonstrate SeroTab's ability to detect pharmacologically induced pH changes (ΔpH = 4, from 2 to 6) and metabolic shifts (42 detected metabolites) following omeprazole administration."
May Evaluation of toxicological profile of omeprazole degradation impurities in an intravenous drug product: omeprazole-sulfone and omeprazole-N-oxide. (Drug and chemical toxicology, 2026, PMID 40719247): "Omeprazole (OMZ) is a widely used proton pump inhibitor for the treatment of acid-related gastrointestinal disorders."
May Omeprazole as a Novel Treatment Option for Giardiasis in Cats. (Veterinary medicine and science, 2026, PMID 42035445): "Recent in vitro studies suggest that omeprazole, a proton pump inhibitor, exhibits anti-giardial effects by inhibiting giardial triosephosphate isomerase."
May Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. (Journal of clinical pharmacology, 2026, PMID 42053447): "...substrates of cytochrome P450 (CYP) 2C19 (omeprazole)..."
Apr Machine learning-driven computational drug repurposing to identify new tubulin inhibitors against cancer. (Bioorganic & medicinal chemistry, 2026, PMID 41689974): "Binding free-energy calculations (MM-GBSA) and 200 ns molecular dynamics simulations identified four stable colchicine-site binders: omeprazole, podofilox, sulfadoxine, and trimethoprim, exhibiting favourable binding energetics."
Apr Pharmacokinetics, Safety, and Tolerability of GS-1427, an Oral Prodrug of a Potent and Selective α4β7 Integrin Inhibitor, in Healthy Participants. (Journal of clinical pharmacology, 2026, PMID 41854177): "Food intake and omeprazole coadministration reduced the exposure to GS-1069518 by approximately 20%-40%."