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Identification
Name Esomeprazole
Accession Number DB00736 (APRD00363)
Type small molecule
Groups approved
Description

A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits the H()-K()-ATPase (H()-K()-exchanging ATPase) in the proton pump of gastric parietal cells. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • esomeprazole
  • Esomeprazole Sodium
  • Esomperazole
Brand names
  • Axagon
  • Esopral
  • Lucen
  • Nexiam
  • Nexium
  • Nexium IV
Brand name mixtures Not Available
Categories
  • Anti-Ulcer Agents
  • Enzyme Inhibitors
  • Proton-pump Inhibitors
  • Antihistamines
CAS number 161796-78-7
Weight Average: 345.416
Monoisotopic: 345.114712179
Chemical Formula C17H19N3O3S
InChI Key InChIKey=SUBDBMMJDZJVOS-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methane]sulfinyl}-1H-1,3-benzodiazole
SMILES
COC1=CC2=C(C=C1)N=C(N2)S(=O)CC1=NC=C(C)C(OC)=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Benzimidazoles
  • Ethers
  • Anisoles
Substructures
  • Phenols and Derivatives
  • Benzimidazoles
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Imines
  • Cyanamides
  • Phenyl Esters
  • 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 Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Mechanism of action Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.
Absorption 90%
Volume of distribution
  • 16 L [healthy volunteers]
Protein binding 97%
Metabolism

Mainly hepatic. Esomeprazole is completely metabolized by the cytochrome P450 system via CYP2C19 and CYP3A4. Metabolism produces inactive hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. Less than 1% of the parent drug is excreted in urine.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2C19 5-hydroxyesomeprazole 5-hydroxylation
Route of elimination Approximately 80% of the administered dose of esomeprazole is excreted as metabolites in urine and the remaining 20% is excreted in feces.
Half life 1-1.5 hours
Clearance Not Available
Toxicity Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00225 Esomeprazole Pathway SMP00225
Pharmacoeconomics
Manufacturers
  • Astrazeneca lp
Packagers
Dosage forms
Form Route Strength
Capsule, delayed release Oral 20 mg
Capsule, delayed release Oral 40 mg
Granule, for suspension Oral 10 mg per packet
Granule, for suspension Oral 20 mg per packet
Granule, for suspension Oral 40 mg per packet
Injection Intravenous 20 mg
Injection Intravenous 40 mg
Prices
Unit description Cost Unit
Nexium i.v. 20 mg vial 33.91 USD vial
Nexium i.v. 40 mg vial 33.91 USD vial
NexIUM 20 mg Delayed Release Capsule 6.76 USD capsule
NexIUM 40 mg Delayed Release Capsule 6.76 USD capsule
Nexium 10 mg packet 6.5 USD each
Nexium 20 mg capsule 6.5 USD capsule
Nexium 20 mg packet 6.5 USD each
Nexium 40 mg capsule 6.5 USD capsule
Nexium 40 mg packet 6.5 USD each
Patents
Country Patent Number Approved Expires
United States 6428810 2000-05-03 2020-05-03
United States 5877192 1994-05-27 2014-05-27
Canada 2346988 2009-02-10 2019-11-03
Canada 1338377 1996-06-11 2013-06-11
Properties
State solid
Melting point 155 oC
Experimental Properties
Property Value Source
water solubility Very slightly soluble in water PhysProp
logP 0.6 PhysProp
Predicted Properties
Property Value Source
water solubility 3.59e-01 g/l ALOGPS
logP 1.66 ALOGPS
logP 2.43 ChemAxon Molconvert
logS -2.98 ALOGPS
pKa 18.29 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 77.10 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 93.66 ChemAxon Molconvert
polarizability 37.45 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Lind T, Rydberg L, Kyleback A, Jonsson A, Andersson T, Hasselgren G, Holmberg J, Rohss K: Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000 Jul;14(7):861-7. Pubmed
External Links
Resource Link
KEGG Drug D01984 Link_out
PubChem Compound 4594 Link_out
PubChem Substance 46504894 Link_out
ChemSpider 4433 Link_out
ChEBI 50275 Link_out
ChEMBL 50275 Link_out
Therapeutic Targets Database DCL000524 Link_out
PharmGKB PA10075 Link_out
Drug Product Database 2244521 Link_out
RxList http://www.rxlist.com/cgi/generic3/esomeprazole.htm Link_out
Drugs.com http://www.drugs.com/cdi/esomeprazole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Esomeprazole Link_out
ATC Codes
  • A02BC05
  • A02BC01
AHFS Codes
  • 56:28.36
PDB Entries Not Available
FDA label show (103.6 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
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. Saccar CL: The pharmacology of esomeprazole and its role in gastric acid related diseases. Expert Opin Drug Metab Toxicol. 2009 Sep;5(9):1113-24. Pubmed
  2. McKeage K, Blick SK, Croxtall JD, Lyseng-Williamson KA, Keating GM: Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults. Drugs. 2008;68(11):1571-607. Pubmed
  3. Vachhani R, Olds G, Velanovich V: Esomeprazole: a proton pump inhibitor. Expert Rev Gastroenterol Hepatol. 2009 Feb;3(1):15-27. Pubmed
  4. 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 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. 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. AstraZeneca. Nexium® (esomeprazole magnesium) delayed-release capsules and packets for delayed-release oral suspension prescribing information. Wilmington, DE; 2008 Dec.
  3. Klotz U: Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther. 2006 Jul;44(7):297-302. Pubmed

2. Cytochrome P450 3A4

Actions: substrate

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. AstraZeneca. Nexium® (esomeprazole magnesium) delayed-release capsules and packets for delayed-release oral suspension prescribing information. Wilmington, DE; 2008 Dec.
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

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.