Esomeprazole

General Description

Esomeprazole (English brand name: Inexium), is the S-isomer of omeprazole. In 1990, in vitro gastric gland model confirmed that two isomers of omeprazole have the same proton pump inhibitory effect. However, it was not possible at that time to prepare a sufficient number of individual isomers for in vivo testing, and the isolated isomers could be slowly racemized in aqueous solution. When sufficient amounts of both isoforms were available for human tesing, the effect of the oral S-isomer was proved to be about 4 times better than that of the R-isomer. Esomeprazole decreases the amount of acid produced in the stomach through specific targeting. It is weakly alkaline and works as a specific inhibitor of proton pumps in parietal cells. Also it concentrates and transforms into an active form in the acid environment of the parietal oxynticus microtubules, thus inhibiting H / K-ATPase (proton pump) of this body part and inhibiting the the secretion of basic gastric acid and stimulated gastric acid. Its curative effects for gastroesophageal reflux disease are better than omeprazole in terms of symptoms relief, inhibition of gastric acid produced in the stomach and promoting the improvement of esophagitis.

Indication

1. Gastroesophageal reflux disease (GERD) is when food or liquid travels from the stomach back up into the esophagus, often causing heartburn, acid reflux, retrosternal pain and other symptoms, and also causing pathologic damage to esophageal mucosa. GERD is one of the common clinical acid-related diseases, and the key to treat the gastroesophageal reflux disease is to inhibit gastric acid secretion. Esomeprazole (eaomeprazole) is the laevo isomer of omeprazole (Nexium), used to treat eflux esophagitis with quick effect and good acid suppression. It can be used alone or in combination with Prokinetic agent or gastrointestinal mucosal protective agent,and its curative effect is better than other PPI (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole),Also it’s safe and effective for the elderly and children infected with reflux esophagitis.
2. Erosive reflux esophagitis treatment
3. Long-term maintenance for healed esophagitis patients.
4. To control symptoms of gastroesophageal reflux disease (GERD) and combine with appropriate antimicrobial therapy to eradicate ofHelicobacter pylori
5. To heal the Helicobacter pylori-related duodenal ulcer
6. To prevent the Helicobacter pylori -related peptic ulcer recurrence.

Usage and Dosage

Swallow the tablet together with the liquid. Don’t chew or crush.

• Gastroesophageal Reflux Disease (GERD)

1. Erosive reflux esophagitis treatment: 40mg once a day. 
Duration of therapy: four weeks.
2. An additional 4 weeks may be considered for patients with esophagitis not healed or the symptoms don’t resolve after initial treatment. Long-term maintenance for healed esophagitis patients: 20mg once a day.
3. Gastroesophageal reflux disease (GERD) symptom control
Patients without esophagitis: 20mg once a day. If symptoms are not controlled after 4 weeks, further examinations should be done to the patient. Once the symptoms have been resolved, 20 mg orally once a day should be taken to maintain the symptom resolution and healing.
4. Combine with appropriate antibiotic therapy to eradicate Helicobacter pylori, heal the Helicobacter pylori-related duodenal ulcer and prevent the Helicobacter pylori -related peptic ulcer recurrence.  
Triple therapy: esomeprazole 20 mg + amoxillin 1 g + clarithromycin 500mg, twice a day. Duration of therapy: 7 days.

Side effects

1. None of the following side effects have been found dose-related. 
2. Common side effects (> 1/100, <1/10): headache, stomach pain, diarrhea, bloating, nausea / vomiting, constipation. 
3. Rare side effects (> 1/1000, <1/100): dermatitis, itching, hives, dizziness, dry mouth. 
4. The following side effects have been observed in the use of racemaic modification (omeprazole), and therefore they may also occur during the use of esomeprazole.

Description

Esomeprazole, formulated as a magnesium salt, reached the market as a treatment for acid-related diseases such as gastro-esophageal reflux (GERD) disease including peptic ulcer disease and reflux esophagitis. Esomeprazole (formerly perprazole) is the active (S)- enantiomer of omeprazole (1988) and the first proton pump inhibitor developed as an optical isomer. It can be obtained by several routes such as asymmetric oxidation of the pro-chiral pyridylmethyl benzimidazole sulfide, separation from the racemic sulfoxide by chiral chromatography or separation of a diastereomeric mixture obtained from the racemic compound and a chiral acid, followed by hydrolysis. Biochemical studies have shown that esomeprazole irreversibly inhibits the gastric H⁺/K⁺-adenosine triphosphatase (ATPase), an enzyme system involved at the secretory surface of the stomach’s parietal cells responsible for the secretion of gastric acid. Compared with racemic omeprazole in healthy subjects, esomeprazole has higher bioavailability, is absorbed more rapidly and exhibits a more uniform and predictable dose-response with higher plasma levels, leading to less inter-individual variability between slow and rapid metabolizers. In extensive clinical trials in patients suffering from GERD symptoms, esomeprazole provided superior acid control and significantly reduced the healing time compared to omeprazole.

Originator

AstraZeneca (UK)

Uses

(-)-Omeprazole can be used to treat migraine.

Uses

Esomeprazole is used to treat certain stomach and esophagus problems (such as acid reflux, ulcers).  It works by decreasing the amount of acid your stomach makes. It  relieves symptoms such as heartburn, difficulty swallowing, and  persistent cough.

Definition

ChEBI: A 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole that has S configuration at the sulfur atom. An inhibitor of gastric acid secretion, it is used (generally as its sodium or magnesium alt) for the treatment of gastro-oesophageal reflux disease, dyspepsia, peptic ulcer disease, and Zollinger-Ellison syndrome.

brand name

Nexium

Drug interactions

Potentially hazardous interactions with other drugs
Anticoagulants: effect of coumarins possibly enhanced.
Antiepileptics: effects of fosphenytoin and phenytoin enhanced.
Antifungals: absorption of itraconazole and ketoconazole reduced; avoid with posaconazole; concentration possibly increased by voriconazole.
Antivirals: concentration of atazanavir and rilpivirine reduced - avoid concomitant use; concentration of raltegravir and saquinavir possibly increased - avoid; concentration of esomeprazole reduced by tipranavir.
Clopidogrel: reduced antiplatelet effect.
Cytotoxics: possibly reduced excretion of methotrexate; avoid with dasatinib, erlotinib and vandetanib; possibly reduced lapatinib absorption; possibly reduced absorption of pazopanib.
Ulipristal: reduced contraceptive effect, avoid with high dose ulipristal

Metabolism

Esomeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma. The major metabolites of esomeprazole have no effect on gastric acid secretion.
Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the faeces. Less than 1% of the parent drug is found in urine.