General
Preferred name
esomeprazole
Synonyms
Esomeprazole (potassium salt) ()
Esomeprazole (magnesium salt) ()
(S)-Omeprazole potassium ()
(-)-Omeprazole magnesium ()
(S)-Omeprazole magnesium ()
NEXIUM ()
Esomeprazole Magnesium ()
(-)-Omeprazole magnesium(S)-Omeprazole magnesium ()
ESOMEPRAZOLE POTASSIUM ()
ESOMEPRAZOLE STRONTIUM ()
(S)-Omeprazole ()
(-)-Omeprazole ()
Esomeprazole magnesium salt ()
Nexium I.V. ()
Inexium paranova ()
Nexium Control ()
Emozul ()
Ventra ()
Omeprazole s-form ()
A02BC05 ()
Omeprazole, (s)- ()
H199/18 Magnesium Trihydrate ()
Nexium 24hr ()
Esomeprazole magnesium hydrate ()
Esomeprazole (as magnesium) ()
Esomeprazole magnesium trihydrate ()
Fm0F67 ()
FM-0F67 ()
Hip1601 ()
S-omeprazole strontium hydrate ()
HIP-1601 ()
NSC-759647 ()
P&D ID
PD010050
CAS
161973-10-0
119141-88-7
217087-09-7
161796-84-5
1198768-91-0
Tags
prodrug
natural product
drug
available
Approved by
FDA
First approval
2013
2001
Drug Status
investigational
approved
Drug indication
Peptic ulcer
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect that persists longer than 24 hours [FDA Label].;
INDICATION
Esomeprazole is indicated for the treatment of acid-reflux disorders including healing and maintenance of erosive esophagitis, and symptomatic gastroesophageal reflux disease (GERD), peptic ulcer disease, H. pylori eradication, prevention of gastrointestinal bleeds with NSAID use, and for the long-term treatment of pathological hypersecretory conditions including Zollinger-Ellison Syndrome.
ROE
The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.
DESCRIPTION
This drug (the S enantiomer) is a component of the approved drug , a racemic mixture of the R and S enantiomers. This drug is a potassium-transporting ATPase inhibitor, commonly referred to as a proton pump inhibitor.
(GtoPdb)
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.; ; Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_. ; ; PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes [A177577, A177580]. ; ; Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life [A177571].
METABOLISM
Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazoleâs metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP3A4 which forms the sulphone metabolite. CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP2C19 and are termed Poor Metabolizers [FDA Label]. However, the influence of CYP 2C19 polymorphism is less pronounced for esomeprazole than for omeprazole[F4495]. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2.; ; Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S- than of the R-isomer [FDA Label]. ; ; Nine major urinary metabolites have been detected. The two main metabolites have been identified as hydroxyesomeprazole and the corresponding carboxylic acid. Three major metabolites have been identified in plasma: the 5-O-desmethyl- and sulphone derivatives and hydroxyesomeprazole. The major metabolites of esomeprazole have no effect on gastric acid secretion[F4495].
ABSORPTION
After oral administration, peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 μmol*hr/L on Day 1 to 11.2 μmol*hr/L on Day 5 after 40 mg once daily dosing. The AUC after administration of a single 40 mg dose of Esomeprazole is decreased by 43% to 53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals[FDA Label].; ; _Combination Therapy with Antimicrobials:_; ; Esomeprazole magnesium 40 mg once daily was given in combination with [DB01211] 500 mg twice daily and [DB01060] 1000 mg twice daily for 7 days to 17 healthy male and female subjects. The mean steady state AUC and Cmax of esomeprazole increased by 70% and 18%, respectively during triple combination therapy compared to treatment with esomeprazole alone. The observed increase in esomeprazole exposure during co-administration with clarithromycin and amoxicillin is not expected to produce significant safety concerns.; ;
DESCRIPTION
The magnesium salt form of Esomeprazole which is a proton pump inhibitor so that could be probably useful in the treatment of sorts of digestive tract diseases through decreasing acid secretion. It was just Launched for Heartburn in USA.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
2
Organisms
1
Compound Sets
17
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
Other bioactive compounds
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
74
Molecular Weight
345.11
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
3
Aromatic Ring Count
3
cLogP
2.9
TPSA
77.1
Fraction CSP3
0.29
Chiral centers
1.0
Largest ring
6.0
QED
0.77
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Proton Pump
H+/K+-ATPase
ATP4A, ATP4B
ATP4A, CLCN2
ATP4A
Bacterial
ATPase,Proton Pump
Pathway
Membrane Transporter/Ion Channel
Anti-infection
MOA
ATPase inhibitor
Proton Pump inhibitor
Indication
gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, peptic ulcer disease (PUD)
gastroesophageal reflux disease (GERD), heartburn
heartburn
Therapeutic Class
Antiulcer Agents
Solubility
10 mM in DMSO
Source data
