Gastric H⁺/K⁺ ATPase (proton pump) – expression detected in MDA-MB-468 triple-negative breast cancer cells by immunofluorescence and Western blotting [1]

Dimethylarginine dimethylaminohydrolase (DDAH) – directly inhibited by PPIs including esomeprazole; no IC50 provided [2]

Inducible nitric oxide synthase (iNOS) – expression downregulated by esomeprazole [2]

Heme oxygenase 1 (HO1) – upregulated by esomeprazole [2]

Keap1/Nrf2 pathway – proposed to be regulated by esomeprazole [2]

By increasing intracellular acidity, esomeprazole (25-100 µM; 20 hours; MDA-MB-468 cells) therapy suppresses triple-negative breast cancer cells' in vitro proliferation in a dose-dependent manner [1].

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Esomeprazole suppressed growth of MDA-MB-468 triple-negative breast cancer cells in a dose-dependent manner with an EC₅₀ of approximately 70 μM after 20 h treatment (trypan blue exclusion assay) [1]

Combination treatment with esomeprazole (30 μM) and doxorubicin (30 nM) significantly improved growth suppression compared to doxorubicin alone (p < 0.05) [1]

Esomeprazole (50 μM, 20 h) increased intracellular acidity in MDA-MB-468 cells, decreasing BCECF-AM fluorescence to 60.2% of control (p < 0.01), comparable to acidified medium pH 6.0 (40.3% of control, p < 0.001) [1]

Non-cancerous MCF-10A breast epithelial cells were significantly less sensitive to esomeprazole: treatment with 100 μM esomeprazole reduced live MCF-10A cells to 92.31% of control (not significant, p = 0.276), whereas MDA-MB-468 cells were reduced to 51.88% of control (p = 0.014) [1]

The C57BL/6J mice treated with esomeprazole (30–300 mg/kg; oral gavage; daily; for 19 or 11 days) showed a significant reduction in the animals' lung fibrosis progression. Additionally, esomeprazole lowers circulating fibrosis and inflammatory markers [2].

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In a mouse model of cotton smoke-induced lung injury (3-week exposure), therapeutic administration of esomeprazole (30 mg/kg, oral, starting day 10 post-exposure) significantly inhibited lung fibrosis progression (mean fibrosis score 0.64 vs. vehicle 1.06, p < 0.05) [2]

The same therapeutic regimen reduced circulating markers of inflammation and fibrosis: plasma TNFα, MMP7 significantly decreased (p < 0.05 vs. vehicle); IL1β showed a decreasing trend [2]

Esomeprazole increased plasma ADMA concentration (p < 0.05 vs. sham) and decreased plasma NO (p < 0.05 vs. vehicle), indicating DDAH inhibition and iNOS suppression in vivo [2]

Prophylactic high-dose esomeprazole (300 mg/kg) was poorly tolerated (increased mortality, bloating, sluggishness) and showed no meaningful anti-fibrotic effect [2]

Cell Viability Assay[1]
Cell Types: MDA-MB-468 Cell
Tested Concentrations: 25 µM, 50 µM, 75 µM, 100 µM
Incubation Duration: 20 hrs (hours)
Experimental Results: Inhibition of triple negative breast cancer cells in a dose-dependent manner in vitro.

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MDA-MB-468 cells were cultured in DMEM supplemented with 10% fetal bovine serum and antibiotics, maintained at 37°C in 5% CO₂. MCF-10A cells were cultured in MEGM mammary epithelial cell growth medium with FBS and antibiotics under same conditions [1]

For cell treatment, cells in 6-well plates were treated for 20 h in FBS-containing RPMI medium (low buffering capacity). After treatment, cells were washed with PBS, trypsinized, mixed with trypan blue solution, and counted using an automated cell counter [1]

For intracellular pH measurement, cells were treated with esomeprazole or acidified medium (pH 6.0), washed with HEPES-buffered saline, incubated with 3 μM BCECF-AM in the same buffer for 30 min at 37°C, then washed. Fluorescence at 530 nm was detected by confocal microscopy and semi-quantified as relative fluorescence per cell [1]

For immunofluorescence, cells grown on glass coverslips were fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton X-100, incubated with mouse anti-human H⁺/K⁺ ATPase β subunit primary antibody, then with FITC-conjugated goat anti-mouse secondary antibody. Fluorescence was detected by confocal microscopy [1]

For Western blotting, cell lysates were analyzed using mouse anti-human H⁺/K⁺ ATPase β subunit primary antibody and HRP-conjugated goat anti-mouse secondary antibody. α-tubulin was used as loading control [1]

Animal/Disease Models: C57BL/6J mice (8 weeks old, 25-30 g) cotton smoke-induced lung injury [2]
Doses: 30 mg/kg, 300 mg/kg
Route of Administration: po (oral gavage); daily; continued for 19 Or 11-day
Experimental Results: Dramatically inhibited the progression of lung fibrosis in animals.

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Cotton smoke-induced lung injury model: 8-week-old C57BL/6J mice (25-30 g) were exposed to cotton smoke for 21 days. Animals were randomized into no-exposure (n=6) and exposure groups. Exposure groups were subdivided into vehicle (n=10, 10% ethanol oral daily), prophylactic esomeprazole (n=10, 300 mg/kg in 10% ethanol oral daily starting day 2 post-exposure), and therapeutic esomeprazole (n=10, 30 mg/kg in 10% ethanol oral daily starting day 10 post-exposure until necropsy) [2]

At necropsy, blood samples were collected by cardiac puncture; lung, liver, heart, and kidney tissues were harvested for organ weight and histopathological comparison. Tissues were fixed in 10% formalin, sectioned, and stained with H&E (inflammation score 1+ to 4+) and Masson‘s Trichrome (fibrosis score 0-8 by Ashcroft system). Blinded evaluation by a board-certified pathologist [2]

Absorption, Distribution and Excretion
Omeprazole extended-release capsules contain enteric-coated omeprazole granules (because omeprazole is unstable in acid), therefore absorption of omeprazole only begins after the granules leave the stomach. Omeprazole is rapidly absorbed, with peak plasma concentrations reached within 0.5–3.5 hours. The absolute bioavailability at doses of 20–40 mg is approximately 30–40% compared to intravenous administration, primarily due to first-pass metabolism. Bioavailability of omeprazole increases slightly with repeated administration of extended-release capsules. Following a single oral dose of omeprazole buffer solution, almost no (or none) of the parent drug is excreted in the urine. The majority of the dose (approximately 77%) is excreted in the urine as at least six distinct metabolites. Two of these metabolites have been identified as hydroxyomeprazole and its corresponding carboxylic acid. The remaining dose is found in the feces. This indicates that omeprazole metabolites are primarily excreted via bile. Three metabolites were identified in plasma: sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole. These metabolites had little or no antisecretory activity. The plasma clearance was approximately 0.3 L/kg, equivalent to the volume of extracellular fluid. In healthy subjects (sustained-release capsules), systemic clearance was 500–600 mL/min; in elderly individuals, plasma clearance was 250 mL/min; and in patients with hepatic impairment, plasma clearance was 70 mL/min. Absorption: Rapid. Distribution: Primarily distributed in tissues, especially gastric parietal cells. Excretion: 72%–80% renally. 18%–23% fecally. Dialysis: Due to extensive protein binding, it is difficult to remove via dialysis. To elucidate the first-pass metabolism of omeprazole in vivo, this study investigated the pharmacokinetics of different doses in rats after oral, duodenal, portal vein, and intravenous administration. The liver and intestinal extractives were calculated based on the area under the concentration-time curve (AUC) for intravenous and intravenous administration, as well as the AUC for intraduodenal and intravenous administration. Assuming complete gastrointestinal absorption, the liver and intestinal extractives were 0.80, 0.63, and 0.59 at doses of 2.5, 5, and 10 mg/kg, respectively; and 0.70 and 0.73 at doses of 5 and 10 mg/kg, respectively. The bioavailability of omeprazole via oral administration was 6.4%, 9.6%, and 12.6% at doses of 10, 20, and 40 mg/kg, respectively. There were no differences in steady-state volume of distribution, total clearance, and elimination half-life among the dose groups. Furthermore, in rats with acute CC(14) poisoning, the AUC of omeprazole administered orally at 20 mg/kg was 2.4 times that of the control group. These results indicate that omeprazole undergoes first-pass metabolism in the intestinal mucosa and/or lumen, as well as in the liver, and the increase in bioavailability with dose is primarily due to the saturation of hepatic first-pass metabolism. Omeprazole is distributed into human breast milk; drug concentrations in breast milk were determined after an oral administration of 20 mg omeprazole to a lactating woman. For more complete data on absorption, distribution, and excretion of omeprazole (6 studies), please visit the HSDB record page. The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of the unchanged drug is excreted in the urine. Approximately 80% of orally administered esomeprazole is excreted in the urine as inactive metabolites, and the remainder is excreted in the feces as inactive metabolites. Esomeprazole binds to plasma proteins at a rate of 97%. Plasma protein binding remains constant within the concentration range of 2 to 20 μmol/L. The apparent volume of distribution in steady-state healthy volunteers is approximately 16 L.
Nexium extended-release capsules and Nexium extended-release oral suspension contain bioequivalent esomeprazole magnesium enteric-coated granules. Bioequivalence is based on a single-dose (40 mg) study conducted in 94 healthy male and female volunteers on an empty stomach. Peak plasma concentration (Cmax) occurred at approximately 1.5 hours (Tmax) after oral administration. Peak plasma concentration (Cmax) increased proportionally with increasing dose, and the area under the plasma concentration-time curve (AUC) tripled from 20 mg to 40 mg. Systemic bioavailability was approximately 90% with repeated once-daily administration of 40 mg, compared to approximately 64% with a single 40 mg dose. The mean exposure (AUC) of esomeprazole increased from 4.32 μmolhr/L on day 1 to 11.2 μmolhr/L on day 5 after once-daily administration of 40 mg.

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Metabolic/Metabolites
Omeprazole is primarily metabolized in the liver via the cytochrome P450 (CYP) enzyme system. Its major metabolism depends on polymorphically expressed CYP2C19, which is responsible for generating hydroxyomeprazole, the major metabolite in plasma. The remaining portion depends on CYP3A4, which is responsible for generating omeprazole sulfone.
To clarify the metabolic pathway of omeprazole and identify the cytochrome P450 (CYP) isoenzymes responsible for generating the major metabolites, we investigated the in vitro metabolism of omeprazole in human liver microsomes.² The four major metabolites identified in vitro (in order of importance) were: hydroxyomeprazole, omeprazole sulfone, 5-O-demethylomeprazole, and one unidentified compound (referred to as metabolite X). We also detected omeprazole pyridinone, but could not quantify it. Incubation of hydroxyomeprazole and omeprazole sulfone with human liver microsomes both generated hydroxysulfone. The formation kinetics of the four major metabolites studied exhibited a biphasic pattern, indicating that each metabolite involves multiple CYP isoenzymes. Subsequent studies employed substrate concentrations with predominantly high affinity activity. The formation of the major metabolite hydroxyomeprazole was significantly correlated with S-mephenytoin hydroxylase, benzo[a]pyrene metabolism, and CYP3A levels. Inhibition studies using isoenzyme-selective inhibitors also showed that S-mephenytoin hydroxylase plays a dominant role in the formation of hydroxyomeprazole, with CYP3A also contributing. The correlation and inhibition data between sulfone compounds and metabolite X are consistent with the view that the CYP3A subfamily plays a dominant role in the formation of these metabolites. R, S-mephenytoin, and quinidine all inhibited the formation of 5-O-demethylomeprazole, suggesting that S-mephenytoin hydroxylase and CYP2D6 may mediate this reaction in human liver microsomes and in vivo. The Vmax/Km (an indicator of intrinsic clearance) of hydroxyomeprazole is four times that of omeprazole sulfone. Consistent with in vivo studies, this result predicts that omeprazole clearance in individuals with poor mefentoin metabolism will also be reduced due to the decreased clearance of the major metabolite, hydroxyomeprazole. Esomeprazole is primarily metabolized in the liver via the cytochrome P450 (CYP) enzyme system. Esomeprazole metabolites do not possess antisecretory activity. The majority of esomeprazole metabolism depends on the CYP 2C19 isoenzyme, which generates hydroxy and demethylated metabolites. The remainder depends on CYP 3A4, which generates sulfone metabolites. The CYP 2C19 isoenzyme exhibits polymorphism in esomeprazole metabolism, as approximately 3% of Caucasians and 15% to 20% of Asians lack CYP 2C19 and are termed astomosomally asthenic. At steady state, the AUC ratio of the weaker metabolizers to that of the rest of the population (stronger metabolizers) is approximately 2. After administration of equimolar doses, the S- and R-isomers are metabolized differently in the liver, resulting in higher plasma concentrations of the S-isomer than the R-isomer. Known metabolites of omeprazole include 3-hydroxyomeprazole, 5-hydroxyomeprazole, omeprazole sulfone, and 5'-O-demethylomeprazole. The liver is the primary metabolic pathway for omeprazole, primarily via the cytochrome P450 (CYP) enzyme system. The two main CYP isoenzymes involved in this metabolism are CYP2C19 and CYP3A4. Metabolism is stereoselective, with the S-isomer being converted to 5'-O-demethylomeprazole via CYP2C19. CYP3A4 converts the S-isomer to 3-hydroxyomeprazole. The R-isomer is converted to 5-hydroxyomeprazole via CYP2C19. CYP3A4 converts the R-isomer into four distinct metabolites: 5-hydroxyomeprazole (5-OH OME), omeprazole sulfone (OME sulfone), 5'-O-demethylomeprazole (5'-demethylOME), and 3-hydroxyomeprazole (3-OH OME). Elimination pathway: Urinary excretion is the primary route of excretion for omeprazole metabolites. Almost no unchanged drug is excreted in the urine. The majority of the dose (approximately 77%) is excreted in the urine as at least six metabolites. Two of these metabolites have been identified as hydroxyomeprazole and its corresponding carboxylic acid. The remaining dose is excreted in the feces. Half-life: 0.5–1 hour (healthy subjects, extended-release capsules); 3 hours (hepatic impairment)
Biological half-life
0.5–1 hour (healthy subjects, extended-release capsules); approximately 3 hours (hepatic impairment)
Plasma - Normal liver function - 30 minutes to 1 hour. Chronic liver disease - 3 hours.

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Esomeprazole is administered as a prodrug. In the stomach, acidic microenvironment (pH <5) triggers chemical rearrangement into sulfenic acids or sulfonamide analogs to block gastric H⁺/K⁺ ATPase. At higher pH (>6.1), no appreciable conversion occurs [2]

The study was conducted in mice, which do not have a physiologic reflux response, suggesting that the prodrug itself may be active in modulating lung inflammation and fibrosis [2]

Toxicity Summary
Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion by specifically inhibiting the H+/K+-ATPase in gastric parietal cells. Omeprazole reduces gastric acidity by specifically acting on the proton pump, blocking the final step in gastric acid formation. Interactions
Omeprazole, especially at high doses, inhibits the cytochrome P450 enzyme system, thereby reducing hepatic metabolism of coumarin or indanedione derivative anticoagulants, diazepam, or phenytoin. Concomitant use of these drugs with omeprazole may result in delayed drug clearance and elevated blood concentrations. Omeprazole may increase gastrointestinal pH; concomitant use with ampicillin esters, iron salts, or ketoconazole may reduce the absorption of these drugs. Concomitant administration of omeprazole and myelosuppressants may enhance the leukopenic and/or thrombocytopenic effects of both drugs; if concomitant administration is necessary, close monitoring for toxicity is essential. This study investigated the effects of omeprazole on drug metabolism using the model drugs antipyrine and 14C-aminopyrine. In male subjects, clearance of both model drugs was assessed 15 days before and after treatment. The study concluded that omeprazole does not metabolically inhibit the model drugs at normal clinical doses. For more complete data on interactions of omeprazole (9 in total), please visit the HSDB record page. In a single-dose study, concomitant administration of 20 mg omeprazole and 1 g sucralfate resulted in delayed omeprazole absorption and a 16% reduction in bioavailability. Proton pump inhibitors should be taken at least 30 minutes before sucralfate. Pharmacokinetic interactions exist with omeprazole (reducing plasma concentrations and AUC of rilpivirine). ^{32 343} Concomitant use with other proton pump inhibitors may also lead to a decrease in rilpivirine plasma concentrations. ³⁴³ Concomitant use of rilpivirine with proton pump inhibitors is contraindicated.
Opposing once-daily 40 mg omeprazole with atazanavir (whether or not in combination with low-dose ritonavir) can result in a significant decrease in atazanavir plasma concentrations and may lead to loss of efficacy or the development of resistance to antiretroviral drugs. Concomitant administration of omeprazole 40 mg once daily (taken 2 hours before atazanavir) and atazanavir 400 mg once daily reduced the AUC and peak plasma concentration of atazanavir by 94% and 96%, respectively. The manufacturer of esomeprazole states that concomitant use with atazanavir is not recommended. If atazanavir is used in patients who have not previously received antiretroviral therapy and are currently taking a proton pump inhibitor (PPI), a ritonavir-boosting regimen is recommended: atazanavir 300 mg once daily, combined with ritonavir 100 mg once daily, taken with food. The PPI should be taken approximately 12 hours before the ritonavir-boosting atazanavir; the PPI dose should not exceed omeprazole 20 mg once daily (or an equivalent dose). Concomitant use of a PPI and atazanavir is not recommended for patients who have previously received antiretroviral therapy. In healthy individuals, once-daily administration of 20 mg omeprazole and digoxin can increase the bioavailability of digoxin by 10% (up to 30% in some individuals). Because esomeprazole is the enantiomer of omeprazole, it is expected that co-administration of esomeprazole with digoxin will increase systemic exposure to digoxin; therefore, monitoring for symptoms of digoxin poisoning may be necessary during concurrent use of esomeprazole and digoxin. For more complete data on interactions of esomeprazole (7 types), please visit the HSDB record page. Non-human toxicity values: Mouse intravenous LD50: 0.08 g/kg; Mouse oral LD50: >4 g/kg; Rat intravenous LD50: >0.05 g/kg; Rat oral LD50: >4 g/kg

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PPIs including esomeprazole are generally well tolerated with mild and transient side effects; most common are headache and diarrhea [1]

High doses up to 240 mg IV daily have been used with good tolerability in Zollinger-Ellison syndrome (standard doses 10-40 mg) [1]

Potential problems with long-term use of high doses are unknown due to lack of studies [1]

In mice, high-dose esomeprazole (300 mg/kg) caused bloating, sluggishness, and increased mortality; low dose (30 mg/kg) was well tolerated [2]

Liver showed a slight but non-significant increase in weight in esomeprazole-treated groups (p > 0.05) [2]

Lethal dose in rodents is generally above 1 g/kg body weight [2]

[1]. Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers. An introductory study. J Pharm Pharm Sci. 2014;17(3):439-46.

[2]. Therapeutic Efficacy of Esomeprazole in Cotton Smoke-Induced Lung Injury Model. Front Pharmacol. 2017 Jan 26;8:16.

[3]. Esomeprazole: a clinical review. Am J Health Syst Pharm. 2002 Jul 15;59(14):1333-9.

Therapeutic Uses
Omeprazole is indicated for the treatment of a range of symptoms caused by any condition requiring a reduction in gastric acid secretion (e.g., duodenal ulcers, gastric ulcers, NSAID-associated gastric and duodenal ulcers, reflux esophagitis, gastroesophageal reflux disease), or symptoms without a definite organic cause (i.e., functional dyspepsia). /US Product Label Includes/ Omeprazole is indicated for the treatment of heartburn and other symptoms associated with gastroesophageal reflux disease. Omeprazole is indicated for short-term treatment of endoscopically diagnosed erosive esophagitis (associated with gastroesophageal reflux disease). Omeprazole is also indicated for maintaining the healing of erosive esophagitis. /US Product Label Includes/ Omeprazole is indicated for long-term treatment of pathological hyperacidity associated with Zollinger-Ellison syndrome (alone or as part of type 1 multiple endocrine neoplasia), systemic mastocytosis, and multiple endocrine adenomas. /Included on US Product Label/
For more complete data on the therapeutic uses of omeprazole (8 types), please visit the HSDB record page.
Anti-ulcer drug; Proton pump inhibitor
Although evidence is currently limited, proton pump inhibitors have been used to suppress gastric acid secretion as adjunctive therapy for symptoms of upper gastrointestinal Crohn's disease (including esophageal, gastroduodenal, and jejunal diseases).^{22 23 24 25 26 27 28}To date, most evidence of efficacy comes from case studies of patients with Crohn's disease-related peptic ulcers who have not responded to other therapies, such as H2 receptor antagonists, cytoprotective agents, antacids, and/or sucralfate. /Not Included on Product Label/
Esomeprazole magnesium is used for long-term treatment of pathological gastrointestinal hypersecretion states. An open-label study in a small number of patients with a prior diagnosis of pathological gastrointestinal hypersecretion disorders (e.g., Zollinger-Ellison syndrome, idiopathic hyperacidity) confirmed the efficacy of this indication; patients received a total daily dose of esomeprazole ranging from 80 mg to 240 mg. During the 12-month study period, these doses were generally well tolerated by patients. After 12 months of treatment, baseline gastric acid output (BAO) was controlled in 90% of patients treated with esomeprazole, defined as BAO less than 5 mEq/hour in patients who had previously undergone gastric acid reduction surgery, and less than 10 mEq/hour in patients who had not undergone gastric acid reduction surgery. Esomeprazole magnesium is used to reduce the risk of gastric ulcers in patients on long-term nonsteroidal anti-inflammatory drugs (NSAIDs), including older adults aged 60 years and/or patients with a history of gastric ulcer disease. Two 6-month randomized controlled trials confirmed the efficacy of esomeprazole magnesium for this indication. These studies enrolled patients receiving long-term therapy with typical NSAIAs or selective cyclooxygenase-2 (COX-2) inhibitors. Participants were considered at risk for developing NSAIA-related ulcers due to their age (60 years or older) and/or a history of gastric or duodenal ulcers within the past 5 years, but no evidence of gastric or duodenal ulcers was found on endoscopy at the start of the studies. The results showed that daily administration of 20 or 40 mg esomeprazole was superior to placebo in preventing gastric ulcer development during the 6-month treatment period; however, no additional benefit was observed at the daily 40 mg dose compared to the 20 mg dose. In these studies, 94.7% to 95.4% of patients treated with 20 mg esomeprazole daily were ulcer-free; 95.3% to 96.7% of patients treated with 40 mg esomeprazole daily were ulcer-free; and 83.3% to 88.2% of patients treated with placebo were ulcer-free. These results were confirmed by serial endoscopy over a period of 6 months. The incidence of duodenal ulcers was too low to determine the effect of esomeprazole treatment on the development of duodenal ulcers. For more complete data on the therapeutic uses of esomeprazole (6 types), please visit the HSDB record page. Drug Warnings: Pregnancy Risk Grade: C/Risk cannot be ruled out. There are currently insufficient, well-controlled human studies, and animal studies have not shown any risk to the fetus or lack relevant data. There is a possibility of fetal harm if this drug is taken during pregnancy; however, the potential benefits may outweigh the potential risks. Currently, there is no information regarding the relationship between age and the efficacy of omeprazole in elderly patients. However, drug clearance may be slightly reduced and bioavailability may be increased in elderly patients taking omeprazole. Omeprazole is generally well tolerated. The most common adverse reactions associated with omeprazole treatment involve the gastrointestinal tract (e.g., diarrhea, nausea, constipation, abdominal pain, vomiting) and the central nervous system (e.g., headache, dizziness). Diarrhea, abdominal pain, nausea, vomiting, constipation, bloating, and acid reflux are the most common gastrointestinal adverse reactions to omeprazole, occurring in approximately 1–5% of cases. Adverse reactions such as dysphagia, bloating, anorexia, irritable bowel syndrome, stool discoloration, pancreatitis (sometimes fatal), esophageal candidiasis, tongue mucosal atrophy, taste disturbance, and dry mouth have been reported occasionally, but in many cases are not directly caused by the drug. Reports of benign gastric fundic polyps are rare and appear to subside upon discontinuation of omeprazole treatment.
For more complete data on drug warnings for omeprazole (15 in total), please visit the HSDB record page.
It is currently unknown whether esomeprazole is excreted into breast milk. However, omeprazole is excreted into human breast milk; breastfeeding should be discontinued or the drug should be discontinued due to the potential risk to the nursing infant.
FDA Pregnancy Category: B / No evidence of risk to humans. Although adverse reactions have been observed in animal studies, adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal malformations; or, in the absence of adequate human studies, animal studies have shown no fetal risk. The possibility of fetal harm is small but still exists. /
When esomeprazole is used in combination with naproxen fixed-dose formulations, the usual precautions, precautions, and contraindications for naproxen must be considered in addition to the precautions, precautions, and contraindications associated with esomeprazole.
Taking proton pump inhibitors is associated with an increased risk of certain infections, such as community-acquired pneumonia. For more complete data on esomeprazole (12 in total), please visit the HSDB record page. Pharmacodynamics Effects on Gastric Acid Secretion This drug reduces gastric acid secretion. After oral administration of omeprazole, its acid-suppressing effect typically begins within 1 hour and reaches its maximum effect 2 hours after administration. Repeated once-daily dosing enhances the inhibitory effect of omeprazole on gastric acid secretion, reaching a plateau after 4 days. Effects on Serum Gastrin In studies involving 200 or more patients, serum gastrin levels increased during the first 1–2 weeks of daily treatment with therapeutic doses of omeprazole. This occurred concurrently with the inhibition of gastric acid secretion. Continued use of omeprazole did not result in further increases in serum gastrin levels. Elevated gastrin levels can lead to enterochromaffin cell proliferation and elevated serum chromogranin A (CgA) levels. Elevated CgA levels may lead to false-positive results on diagnostic tests for neuroendocrine tumors. Enterochromaffin-like Cell (ECL) Effects In long-term clinical studies, gastric biopsy samples have been obtained from over 3,000 pediatric and adult patients treated with omeprazole. The incidence of ECL hyperplasia increased over time in these studies; however, no cases of ECL cell carcinoids, dysplasia, or tumors were found in these patients. However, the sample size and duration of these studies are insufficient to draw conclusions regarding the potential impact of long-term omeprazole use on the development of any precancerous lesions or malignancies. Other Effects To date, no systemic effects of omeprazole on the central nervous system, cardiovascular system, or respiratory system have been observed. Oral administration of omeprazole 30 or 40 mg for 2–4 weeks has no effect on thyroid function, carbohydrate metabolism, or circulating parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin, or secretin levels.

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Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors, making hormone-based therapies ineffective. Doxorubicin use is limited by dose-dependent cardiotoxicity. This study provides first evidence that adjunct use of esomeprazole may combat doxorubicin‘s adverse effects and increase its effectiveness [1]

Esomeprazole increases intracellular acidification of cancer cells, which correlates with decreased growth and survival. Gastric H⁺/K⁺ ATPase expression in breast cancer cells was previously unreported [1]

PPIs contain a benzimidazole scaffold, considered a “privileged” structure that can target multiple biological molecules. About 25% of the 100 best-selling drugs incorporate a benzimidazole moiety [2]

PPIs have been shown to inhibit DDAH enzymatic activity, downregulate iNOS and other proinflammatory molecules (TNFα, interleukins, adhesion molecules), and upregulate HO1. These effects may be mediated via the Keap1/Nrf2 pathway [2]

Retrospective clinical studies have reported that PPI use is associated with favorable outcomes in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including greater DLCO, prolonged transplant-free survival, fewer acute exacerbations, and reduced mortality [2]

The American Thoracic Society (ATS) issued a conditional recommendation for IPF patients to be treated with PPIs regardless of GERD status [2]

Since mice do not have a reflux response, the observed anti-inflammatory and anti-fibrotic effects of esomeprazole in the smoke-induced lung injury model are not mediated by GERD mechanisms, suggesting direct modulation of lung injury pathways [2]

C17H19N3O3S

345.417

345.114

119141-88-7

Esomeprazole magnesium trihydrate;217087-09-7;Esomeprazole sodium;161796-78-7;Esomeprazole magnesium;161973-10-0;Esomeprazole magnesium salt;1198768-91-0;Esomeprazole potassium salt;161796-84-5;Esomeprazole hemistrontium;914613-86-8;Esomeprazole-d3 sodium;Esomeprazole-d3

4594

Crystals from acetonitrile
White to off-white crystalline powder

1.4±0.1 g/cm3

600.0±60.0 °C at 760 mmHg

316.7±32.9 °C

0.0±1.7 mmHg at 25°C

1.669

2.17

1

6

5

24

453

0

O=[S@](C1=NC2=CC=C(OC)C=C2N1)CC3=NC=C(C)C(OC)=C3C

SUBDBMMJDZJVOS-UHFFFAOYSA-N

InChI=1S/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)

1H-Benzimidazole, 5-methoxy-2-((S)-((4-methoxy-3,5-dimethyl-2- pyridinyl)methyl)sulfinyl)-

Esomeprazole (–) Omeprazole(–)-Omeprazole (S) Omeprazole (S)-Omeprazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~361.88 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)