Following a 16-hour exposure to 0.2 mM of rabeprazole, human gastric cancer cells exhibit reduced vitality [2]. In MKN-28 cells, rabeprazole totally suppressed ERK1/2 phosphorylation. For two hours, the gastric cancer cell line MKN-28 was grown in an acidic media (pH 5.4). In MKN-28 cells, rabeprazole pretreatment (0.2 mM, 2 hours) significantly reduced ERK1/2 phosphorylation [2].

In female mice, courses of rabeprazole (10 mg/kg; oral; every 48 hours for 18 weeks) led to significant reductions in serum calcium levels, secondary parathyroid disease, and bone mineral density (BMD). hyperthyroidism [3].

Cell Viability Assay[2]
Cell Types: Three gastric cancer cell lines KATO III, MKN-28 and MKN-45
Tested Concentrations: 0.2 mM
Incubation Duration: 16 hrs (hours)
Experimental Results: Treatment resulted in diminished viability of all cancer cell lines tested, with KATO III and Compared with MKN-45 cells, the cell viability of MKN-28 cells was Dramatically diminished.

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Cell viability assay[2]
Cell Types: Three gastric cancer cell lines (KATO III, MKN-28 and MKN-45)[2]
Tested Concentrations: 0.2 mM
Incubation Duration: 2 hrs (hours) pretreatment
Experimental Results: Result in strong inhibition of ERK 1/2 Phosphorylated in MKN-28 cells, but no similar effect was observed in KATO III and MKN-45 cells.

Animal/Disease Models: Female Swiss albino mice (body weight 18-26 g) [3]
Doses: 10 mg/kg
Route of Administration: Oral; every 48 hrs (hrs (hours)) for 18 weeks
Experimental Results: Serum calcium levels compared with vehicle-treated group Dramatically lower (5.5±2.07 vs. 9.68±2.77).

Absorption, Distribution and Excretion
Absolute bioavailability is approximately 52%.
Following a single 20 mg oral dose of 14C-labeled rabeprazole, approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites.
Elimination: Normal renal function: Approximately 1 to 2 hours. Hepatic function impairment: 2 to 6 hours.
Protein binding: Very high; approximately 96% bound to human plasma protein.
Since rabeprazole is acid-labile, it is administered as a delayed-release tablet so that it can pass through the stomach relatively intact. Once rabeprazole has left the stomach, absorption occurs within 1 hour of administration. The bioavailability is approximately 52%.
It is unknown whether rabeprazole is distributed into human milk. However, in lactating rats, levels of rabeprazole were 2 to 7 times higher in milk than in blood.
For more Absorption, Distribution and Excretion (Complete) data for RABEPRAZOLE (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic
Approximately 90% of the rabeprazole dose is excreted in the urine as metabolites. These metabolites are mainly thioether carboxylic acid (TCA), the glucuronide of TCA, and mercapturic acid.
Rabeprazole is extensively metabolized. The thioether and sulphone are the primary metabolites measured in human plasma. These metabolites were not observed to have significant antisecretory activity. In vitro studies have demonstrated that rabeprazole is metabolized in the liver primarily by cytochromes P450 3A (CYP3A) to a sulphone metabolite and cytochrome P450 2C19 (CYP2C19) to desmethyl rabeprazole. The thioether metabolite is formed non-enzymatically by reduction of rabeprazole. CYP2C19 exhibits a known genetic polymorphism due to its deficiency in some sub-populations (e.g. 3 to 5% of Caucasians and 17 to 20% of Asians). Rabeprazole metabolism is slow in these sub-populations, therefore, they are referred to as poor metabolizers of the drug.
Rabeprazole is a known human metabolite of Rabeprazole (rabeprazole_thioether).

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Biological Half-Life
1-2 hours (in plasma)
The plasma half-life ranges from 1 to 2 hours.
The study was designed to determine the absolute bioavailability of 20 mg rabeprazole tablets in normal, healthy subjects in comparison with intravenous administration of 20 mg rabeprazole. ... Each subject was randomized at the beginning of the study to receive either a single 20 mg dose of rabeprazole intravenously or orally during Period 1. ... Intravenous dose was given in constant infusion over five minutes. ... The elimination half-life of rabeprazole sodium (1.47 +/- 0.82 hr) after oral administration was significantly longer than the elimination half-life after intravenous administration (1.02 +/- 0.63 hr), probably due to slower rate of absorption than that of elimination.

Hepatotoxicity
Despite its wide use, rabeprazole has only rarely been associated with hepatic injury. In large scale, long term trials of rabeprazole, serum ALT elevations occurred in less than 1% of patients and at rates similar to those with placebo or comparator drugs. In large case series of drug induced liver injury, rabeprazole has accounted for few instances of symptomatic acute liver injury. Only a few cases of clinically apparent liver disease due to rabeprazole have been published and the characteristics of the injury have not been well defined, but appear to be similar to the features of hepatic injury associated with other proton pump inibitors. Clinically apparent liver injury due to proton pump inhibitors typically arises within the first 4 weeks of treatment with symptoms of jaundice, nausea and fatigue and a hepatocellular or mixed pattern of serum enzyme elevations. Recovery is typically rapid upon withdrawal of the agent. Rash, fever and eosinophilia are rare, as is autoantibody formation. Instances of recurrence on rechallenge have been reported.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of rabeprazole during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
A retrospective claims database study in the United States found that users of proton pump inhibitors had an increased risk of gynecomastia.
The Spanish pharmacovigilance system found one case of a 90-year-old man who developed gynecomastia associated with rabeprazole reported during the time period of 1982 to 2006. The reaction occurred after 32 days of therapy and resolved after discontinuation of the drug.
A review article reported that a search of database from the European Pharmacovigilance Centre found 11 cases of gynecomastia, 3 cases of galactorrhea, 2 cases of breast pain and 1 case of breast enlargement associated with rabeprazole. A search of the WHO global pharmacovigilance database found 38 cases of gynecomastia, 29 cases of galactorrhea, 28 cases of breast pain and 5 cases of breast enlargement associated with rabeprazole.
A woman was prescribed metronidazole 400 mg three times a day, and a combination product containing rabeprazole 20 mg and domperidone 30 mg daily for diarrhea and dyspepsia. After 3 days of treatment,
she developed bilateral galactorrhea. The combination of rabeprazole and domperidone was thought to be the cause.

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Protein Binding
96.3% (bound to human plasma proteins)

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Interactions
Warfarin: Potential pharmacokinetic interaction. Proton-pump inhibitors may inhibit warfarin metabolism. No clinically important interaction in single-dose studies, but increased international normalized ration (INR) and prothrombin time (PT) have been reported in patients receiving these drugs concomitantly; may need to monitor INR and PT during concomitant use with rabeprazole.
Rabeprazole may increase gastrointestinal pH; concurrent use /of digoxin/ with rabeprazole resulted in increase of the serum peak concentration by 29% in normal subjects.
Rabeprazole may increase gastrointestinal pH; concurrent use /of ketoconazole/ with rabeprazole resulted in 30% reduction in bioavailability.
In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the Cmax in healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to that by omeprazole at equivalent concentrations.
Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin.

[1]. Identification of Proton-Pump Inhibitor Drugs That Inhibit Trichomonas Vaginalis Uridine Nucleoside Ribohydrolase. Bioorg Med Chem Lett. 2014 Feb 15;24(4):1080-4.

[2]. Rabeprazole Exhibits Antiproliferative Effects on Human Gastric Cancer Cell Lines. Oncol Lett. 2014 Oct;8(4):1739-1744.

[3]. Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels. Front Pharmacol. 2020 May 13;11:583.

Therapeutic Uses
Antiulcerative
Rabeprazole is indicated for the short-term treatment 4-8 weeks for symptomatic relief and healing of erosive or ulcerative gastroesophageal reflex disease. Rabeprazole may be indicated for an additional 8 weeks of treatment for patients in whom healing has not occurred. Rabeprazole also is indicated to maintain healing of erosive or ulcerative gastroesophageal reflux disease. /Included in US product labeling/
Rabeprazole is indicted for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome. /Included in US product labeling/
Rabeprazole is indicated for short-term treatment (up to 4 weeks) in the healing and symptomatic relief of patients with active duodenal ulcers. /Included in US product labeling/

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Drug Warnings
Caution should be exercised in dosing patients with severe hepatic impairment, particularly because of the lack of clinical data in this patient population. However, accumulation of rabeprazole at the usual dosage of 20 mg daily is unlikely, and dosage adjustment is not necessary in those with mild to moderate hepatic impairment.
Symptomatic response to therapy with rabeprazole does not preclude the occult presence of gastric neoplasm. Approximately 4% of patients had no intestinal metaplasia during follow-up (up to 40 months), with no consistent changes noted.
Administration of proton-pump inhibitors has been associated with an increase risk for developing certain infections (e.g., community-acquired pneumonia).
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./
For more Drug Warnings (Complete) data for RABEPRAZOLE (12 total), please visit the HSDB record page.

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Pharmacodynamics
Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.

C18H21N3O3S

359.4426

359.13

117976-89-3

Rabeprazole sodium;117976-90-6;Rabeprazole-d4;934295-48-4;Rabeprazole Sulfide;117977-21-6

5029

Light green to green solid powder

1.3±0.1 g/cm3

603.9±65.0 °C at 760 mmHg

202-204°C

319.1±34.3 °C

0.0±1.7 mmHg at 25°C

1.655

1.83

1

6

8

25

440

0

YREYEVIYCVEVJK-UHFFFAOYSA-N

InChI=1S/C18H21N3O3S/c1-13-16(19-9-8-17(13)24-11-5-10-23-2)12-25(22)18-20-14-6-3-4-7-15(14)21-18/h3-4,6-9H,5,10-12H2,1-2H3,(H,20,21)

2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)