Pharma Jogot
Esomeprazole is a medication that reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth or injection into a vein.
It was patented in 1993 and approved for medical use in 2000. It is available as a generic medication and sold over the counter in several countries. In 2020, it was the 122nd most commonly prescribed medication in the United States, with more than 5 million prescriptions. It is also available in lower dose formulations without a prescription in the United States, the United Kingdom as well as Australia, Canada, and New Zealand.
Structure:
Physicochemical Data:
| IUPAC Name | (S)-(−)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole |
| CAS Number | 119141-88-7 |
| Molecular Formula | C17H19N3O3S |
| Molecular Mass | 345.42 g·mol−1 |
Pharmacokinetic Data:
| 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 μmolhr/L on Day 1 to 11.2 μmolhr/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. Combination Therapy with Antimicrobials: Esomeprazole magnesium 40 mg once daily was given in combination with Clarithromycin 500 mg twice daily and Amoxicillin 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. |
| Volume of Distribution | The apparent volume of distribution at a steady state in healthy volunteers is approximately 16 L. |
| Protein Binding | Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 to 20 µmol/L. |
| 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 esomeprazole’s 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. However, the influence of CYP 2C19 polymorphism is less pronounced for esomeprazole than for omeprazole. 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. 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 hydroxy esomeprazole. The major metabolites of esomeprazole do not affect gastric acid secretion. |
| Route of Elimination | The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of the 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. |
| Half-life | 1-1.5 hours |
| Clearance | Not Available |
| Toxicity | Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating |
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