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Identification
Name Rabeprazole
Accession Number DB01129 (APRD01212)
Type small molecule
Groups approved
Description

Rabeprazole is an antiulcer drug in the class of proton pump inhibitors. It is a prodrug – in the acid environment of the parietal cells it turns into active sulphenamide form. Rabeprazole inhibits the H+, K+ATPase of the coating gastric cells and dose-dependent oppresses basal and stimulated gastric acid secretion.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Irsogladine Maleate
  • rabeprazole sodium
  • Rebeprazole sodium
Brand names
  • AcipHex
  • Pariet
Brand name mixtures Not Available
Categories
  • Anti-Ulcer Agents
  • Enzyme Inhibitors
CAS number 117976-89-3
Weight Average: 359.443
Monoisotopic: 359.130362243
Chemical Formula C18H21N3O3S
InChI Key InChIKey=YREYEVIYCVEVJK-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methane}sulfinyl)-1H-1,3-benzodiazole
SMILES
COCCCOC1=C(C)C(CS(=O)C2=NC3=C(N2)C=CC=C3)=NC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzimidazoles
  • Ethers
Substructures
  • Benzimidazoles
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Cyanamides
  • Sulfoxides
Pharmacology
Indication For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.
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.
Mechanism of action Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+/K+ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds.
Absorption Absolute bioavailability is approximately 52%.
Volume of distribution Not Available
Protein binding 96.3% (bound to human plasma proteins)
Metabolism

Hepatic
Route of elimination 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.
Half life 1-2 hours (in plasma)
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00229 Rabeprazole Pathway SMP00229
Pharmacoeconomics
Manufacturers
  • Eisai inc
  • Teva pharmaceuticals usa inc
  • Eisai Corporation
Packagers
Dosage forms
Form Route Strength
Tablet, coated Oral
Prices
Unit description Cost Unit
Aciphex 20 mg Enteric Coated Tabs 7.48 USD tab
Aciphex ec 20 mg tablet 6.08 USD tablet
Aciphex 20 mg tablet ec 5.9 USD tablet
Pariet 20 mg Enteric-Coated Tablet 1.46 USD tablet
Apo-Rabeprazole 20 mg Enteric-Coated Tablet 0.82 USD tablet
Novo-Rabeprazole 20 mg Enteric-Coated Tablet 0.82 USD tablet
Pms-Rabeprazole Ec 20 mg Enteric-Coated Tablet 0.82 USD tablet
Ran-Rabeprazole 20 mg Enteric-Coated Tablet 0.82 USD tablet
Sandoz Rabeprazole 20 mg Enteric-Coated Tablet 0.82 USD tablet
Pariet 10 mg Enteric-Coated Tablet 0.73 USD tablet
Apo-Rabeprazole 10 mg Enteric-Coated Tablet 0.41 USD tablet
Novo-Rabeprazole 10 mg Enteric-Coated Tablet 0.41 USD tablet
Pms-Rabeprazole Ec 10 mg Enteric-Coated Tablet 0.41 USD tablet
Ran-Rabeprazole 10 mg Enteric-Coated Tablet 0.41 USD tablet
Sandoz Rabeprazole 10 mg Enteric-Coated Tablet 0.41 USD tablet
Patents
Country Patent Number Approved Expires
United States 5045552 1993-05-08 2013-05-08
Canada 2104531 1999-01-05 2013-08-20
Canada 1336958 1995-09-12 2012-09-12
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 0.6 PhysProp
Predicted Properties
Property Value Source
water solubility 3.36e-01 g/l ALOGPS
logP 2.04 ALOGPS
logP 2.09 ChemAxon Molconvert
logS -3.03 ALOGPS
pKa 17.33 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 77.10 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 98.07 ChemAxon Molconvert
polarizability 39.64 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07864 Link_out
PubChem Compound 5029 Link_out
PubChem Substance 46506366 Link_out
ChemSpider 4853 Link_out
ChEBI 8768 Link_out
ChEMBL 8768 Link_out
Therapeutic Targets Database DAP000727 Link_out
PharmGKB PA451216 Link_out
Drug Product Database 2243797 Link_out
RxList http://www.rxlist.com/cgi/generic3/aciphex.htm Link_out
Drugs.com http://www.drugs.com/cdi/rabeprazole.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/aci1534.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Rabeprazole Link_out
ATC Codes
  • A02BC04
AHFS Codes
  • 56:28.36
PDB Entries Not Available
FDA label show (135.3 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
  • Take without regard to meals. Food may slow absorption rate but extent of absorption is not affected.
Targets

1. Potassium-transporting ATPase alpha chain 1

Pharmacological action: yes
Actions: inhibitor

Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach

Organism class: human
UniProt ID: P20648 Link_out
Gene: ATP4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Langtry HD, Markham A: Rabeprazole: a review of its use in acid-related gastrointestinal disorders. Drugs. 1999 Oct;58(4):725-42. Pubmed
  2. Carswell CI, Goa KL: Rabeprazole: an update of its use in acid-related disorders. Drugs. 2001;61(15):2327-56. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Shimizu M, Uno T, Yasui-Furukori N, Sugawara K, Tateishi T: Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes. Eur J Clin Pharmacol. 2006 Aug;62(8):597-603. Epub 2006 Jun 17. Pubmed
  3. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed

2. Cytochrome P450 2C19

Actions: substrate, inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Shimizu M, Uno T, Yasui-Furukori N, Sugawara K, Tateishi T: Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes. Eur J Clin Pharmacol. 2006 Aug;62(8):597-603. Epub 2006 Jun 17. Pubmed
  4. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed

3. Cytochrome P450 1A1

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A2

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed
  2. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed

6. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed
  2. Li XQ, Andersson TB, Ahlstrom M, Weidolf L: Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 Aug;32(8):821-7. Pubmed
Transporters

1. ATP-binding cassette sub-family G member 2

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y: Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9. Epub 2008 Nov 17. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on June 10, 2011 13:31

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.