General
Preferred name
OMEPRAZOLE
Synonyms
Omeprazole D3 ()
H 16868 D3 ()
H 16868 ()
Losec ()
Prilosec ()
Antra ()
(S)-Omeprazole magnesium trihydrate ()
Esomeprazole Magnesium trihydrate ()
NEXIUM ()
Esomeprazole Magnesium ()
Omeprazole (sodium) ()
OMEPRAZOLE MAGNESIUM ()
OMEPRAZOLE SODIUM ()
H 16868 (sodium) ()
NSC-751450 ()
NSC-759192 ()
H-168/68 ()
Mopral ()
Omeran ()
H 168/68 ()
Mezzopram ()
Losec MUPS ()
Zanprol ()
H 168/68 Magnesium ()
Omeprazole magnesium salt ()
Omeprazole (as magnesium) ()
Prilosec Otc ()
Omeprazole (as sodium) ()
H 168/68 Sodium ()
Losec Sodium ()
Omeprazole-d3 ()
P&D ID
PD000331
CAS
217087-09-7
95510-70-6
161973-10-0
119141-89-8
131959-78-9
922731-01-9
73590-58-6
934293-92-2
Tags
prodrug
drug candidate
natural product
drug
available
Approved by
FDA
First approval
1989
2003
Drug Status
investigational
withdrawn
approved
vet_approved
Drug indication
Antisecretory (gastric)
Antisecretory (gastric),Depressant (gastric acid secretory)
Gastroesophageal reflux disease
Max Phase
Phase 4
Phase 3
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE 0.5-1 hour (healthy subjects, delayed-release capsule) [FDA label] Approximately 3 hours (hepatic impairment) [FDA label]
METABOLISM Omeprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The main part of its metabolism depends on the polymorphically expressed CYP2C19, which is responsible for the formation of _hydroxyomeprazole_, the major metabolite found in plasma. The remaining part depends on CYP3A4, responsible for the formation of _omeprazole sulphone_ [FDA label].
ROE After a single dose oral dose of a buffered solution of omeprazole, negligible (if any) amounts of unchanged drug were excreted in urine. Most of the dose (about 77%) was eliminated in urine as at least six different metabolites. Two metabolites were identified as _hydroxyomeprazole_ and the corresponding _carboxylic acid_. The remainder of the dose was found in the feces. This suggests significant biliary excretion of omeprazole metabolites. Three metabolites have been identified in the plasma, the _sulfide_ and _sulfone_ derivatives of omeprazole, and _hydroxyomeprazole_. These metabolites possess minimal or no antisecretory activity [FDA label].
TOXICITY **Oral acute (LD50)**: 4000 mg/kg (mouse), 2210 mg/kg (rat) [MSDS]. **Overdose** Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth. **Carcinogenesis and mutagenesis** In 24-month studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was seen in male and female animals. Carcinoid tumors have also been found in rats treated with a fundectomy or long-term treatment with other proton pump inhibitors, or high doses of H2-receptor antagonists [FDA label]. Omeprazole showed positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration study, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration test. Omeprazole tested negative in the in vitro _Ames_ test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay [FDA label]. **The use in breastfeeding** Limited data indicate that omeprazole may be present in human milk. There is currently no information on the effects of omeprazole on the breastfed infant or production of milk. The benefits of breastfeeding should be considered along with the level of need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole [FDA label]. **Effects on fertility** Effects of omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose) was found to have no impact on fertility and reproductive performance [FDA label].
HALF-LIFE 0.5-1 hour (healthy subjects, delayed-release capsule) [FDA label] ; Approximately 3 hours (hepatic impairment) [FDA label]
ABSORPTION Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), so that absorption of omeprazole begins only after the granules exit the stomach [FDA label]. Absorption of omeprazole occurs rapidly, with peak plasma concentrations of omeprazole achieved within 0.5-3.5 hours [FDA label]. Absolute bioavailability (compared with intravenous administration) is approximately 30-40% at doses of 20-40 mg, largely due to pre-systemic metabolism. The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules [FDA label].
PHARMACODYNAMICS **Effects on gastric acid secretion**; ; This drug decreases gastric acid secretion [FDA label]. After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days [FDA label].; ; **Effects on serum gastrin**; ; In studies of 200 or more patients, serum gastrin levels increased during the first 1-2 weeks of daily administration of therapeutic doses of omeprazole. This occurred in a parallel fashion with the inhibition of acid secretion. No further increase in serum gastrin occurred with continued omeprazole administration. Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may lead to false positive results in diagnostic studies for neuroendocrine tumors [FDA label].; ; **Enterochromaffin-like (ECL) cell effects**; ; Human gastric biopsy samples have been obtained from more than 3000 pediatric and adult patients treated with omeprazole in long-term clinical studies. The incidence of enterochromaffin-like cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia have been identified in these patients. These studies, however, are of insufficient in power and duration to draw conclusions on the possible influence of long-term administration of omeprazole in the development of any premalignant or malignant conditions [FDA label]. ; ; **Other effects**; ; Systemic effects of omeprazole in the central nervous system, cardiovascular and respiratory systems have not been found to date. Omeprazole, given in oral doses of 30 or 40 mg for 2-4 weeks, showed no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin [FDA label]. ; ; ;
INDICATION Omeprazole, according to the FDA label [FDA label] is a proton pump inhibitor (PPI) used for the following purposes:; ; • Treatment of active duodenal ulcer in adults ; ; • Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer; recurrence in adults ; ; • Treatment of active benign gastric ulcer in adults ; ; • Treatment of symptomatic gastroesophageal reflux disease (GERD) in; patients 1 year of age and older ; ; • Treatment of erosive esophagitis (EE) due to acid-mediated GERD in; patients 1 month of age and older ; ; • Maintenance of healing of EE due to acid-mediated GERD in patients 1; year of age and older ; ; • Pathologic hypersecretory conditions in adults
ABSORPTION Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), so that absorption of omeprazole begins only after the granules exit the stomach [FDA label]. ; ; Absorption of omeprazole occurs rapidly, with peak plasma concentrations of omeprazole achieved within 0.5-3.5 hours [FDA label]. ; ; Absolute bioavailability (compared with intravenous administration) is approximately 30-40% at doses of 20-40 mg, largely due to pre-systemic metabolism. The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules [FDA label].
DESCRIPTION This approved drug omeprazole is a racemic mixture of the R and S stereoisomers. Omeprazole is a potassium-transporting ATPase inhibitor, commonly referred to as a proton pump inhibitor. (GtoPdb)
PHARMACODYNAMICS **Effects on gastric acid secretion** This drug decreases gastric acid secretion [FDA label]. After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days [FDA label]. **Effects on serum gastrin** In studies of 200 or more patients, serum gastrin levels increased during the first 1-2 weeks of daily administration of therapeutic doses of omeprazole. This occurred in a parallel fashion with the inhibition of acid secretion. No further increase in serum gastrin occurred with continued omeprazole administration. Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may lead to false positive results in diagnostic studies for neuroendocrine tumors [FDA label]. **Enterochromaffin-like (ECL) cell effects** Human gastric biopsy samples have been obtained from more than 3000 pediatric and adult patients treated with omeprazole in long-term clinical studies. The incidence of enterochromaffin-like cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia have been identified in these patients. These studies, however, are of insufficient in power and duration to draw conclusions on the possible influence of long-term administration of omeprazole in the development of any premalignant or malignant conditions [FDA label]. **Other effects** Systemic effects of omeprazole in the central nervous system, cardiovascular and respiratory systems have not been found to date. Omeprazole, given in oral doses of 30 or 40 mg for 2-4 weeks, showed no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin [FDA label].
MOA Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump [A175180], expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid) [A174295]. Omeprazole is a member of a class of antisecretory compounds, the substituted _benzimidazoles_, that stop gastric acid secretion by selective inhibition of the _H+/K+ ATPase_ enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the _H+/K+ ATPase_ pump, inhibiting gastric acid secretion for up to 36 hours [A175192]. This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus [FDA label]. **Mechanism of H. pylori eradication** Peptic ulcer disease (PUD) is frequently associated with _Helicobacter pylori_ bacterial infection (NSAIDs) [A175195]. The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimen [FDA label], [A175198]. _H. pylori_ replicates most effectively at a neutral pH [A175213]. Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori [A175198]. It is generally believed that proton pump inhibitors inhibit the _urease_ enzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions [A175216].
INDICATION Omeprazole, according to the FDA label [FDA label] is a proton pump inhibitor (PPI) used for the following purposes: • Treatment of active duodenal ulcer in adults • Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults • Treatment of active benign gastric ulcer in adults • Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and older • Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 1 month of age and older • Maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older • Pathologic hypersecretory conditions in adults
MOA Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump [A175180], expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid) [A174295].; ; Omeprazole is a member of a class of antisecretory compounds, the substituted _benzimidazoles_, that stop gastric acid secretion by selective inhibition of the _H+/K+ ATPase_ enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the _H+/K+ ATPase_ pump, inhibiting gastric acid secretion for up to 36 hours [A175192]. This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus [FDA label]. ; ; **Mechanism of H. pylori eradication**; ; Peptic ulcer disease (PUD) is frequently associated with _Helicobacter pylori_ bacterial infection (NSAIDs) [A175195]. The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimen [FDA label], [A175198]. ; _H. pylori_ replicates most effectively at a neutral pH [A175213]. Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori [A175198]. It is generally believed that proton pump inhibitors inhibit the _urease_ enzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions [A175216].
TOXICITY **Oral acute (LD50)**: 4000 mg/kg (mouse), 2210 mg/kg (rat) [MSDS]. ; ; **Overdose**; ; Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth.; ; **Carcinogenesis and mutagenesis**; ; In 24-month studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was seen in male and female animals. Carcinoid tumors have also been found in rats treated with a fundectomy or long-term treatment with other proton pump inhibitors, or high doses of H2-receptor antagonists [FDA label].; ; Omeprazole showed positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration study, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration test. Omeprazole tested negative in the in vitro _Ames_ test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay [FDA label].; ; **The use in breastfeeding**; ; Limited data indicate that omeprazole may be present in human milk. There is currently no information on the effects of omeprazole on the breastfed infant or production of milk. The benefits of breastfeeding should be considered along with the level of need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole [FDA label]. ; ; **Effects on fertility**; ; Effects of omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose) was found to have no impact on fertility and reproductive performance [FDA label].
DESCRIPTION H+,K+-ATPase inhibitor (Tocriscreen Total)
DESCRIPTION Potent FLT3 inhibitor (Tocris Bioactive Compound Library)
Cell lines
2
Organisms
9
Compound Sets
33
AdooQ Bioactive Compound Library
A10672
Cayman Chemical Bioactives
14880
22087
ChEMBL Approved Drugs
CHEMBL1503
CHEMBL1567328
ChEMBL Drugs
CHEMBL1503
CHEMBL2105294
CHEMBL1567328
Concise Guide to Pharmacology 2017/18
4279
Concise Guide to Pharmacology 2019/20
4279
Concise Guide to Pharmacology 2021/22
4279
Concise Guide to Pharmacology 2023/24
4279
DrugBank
DB00338
DrugBank Approved Drugs
DB00338
DrugCentral
1990
DrugCentral Approved Drugs
1990
DrugMAP
DM471KJ
DrugMAP Approved Drugs
DM471KJ
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101645
Guide to Pharmacology
4279
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1503
MedChem Express Bioactive Compound Library
HY-B0113
HY-B0113A
Natural product-based probes and drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Omeprazole
omeprazole-sodium
TargetMol Bioactive Compound Library
T0757
T8386
The Spectrum Collection
Tocris Bioactive Compound Library
2583
Tocriscreen Total
Withdrawn 2.0
w184
External IDs
133
Properties
(calculated by RDKit )
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
Bacterial
Phospholipase
ATPase,Autophagy,Proton Pump
P450 (e.g. CYP17),Proton Pump
Pathway
Membrane Transporter/Ion Channel
Autophagy
Anti-infection
Metabolic Enzyme/Protease
Primary Target
H+,K+-ATPase
MOA
Inhibitor
ABCC3 Expression Enhancers
H+/K+-ATPase Inhibitors
Member status
virtual
ATC
A02BC01
Toxicity type
neurological
Therapeutic Indication
Antiulcer
Therapeutic Class
Antiulcer Agents
Source data