It Is Used To Treat Symptoms Of Gastroesophageal Reflux Disease (GERD) And Other Conditions Involving Excessive Stomach Acid Such As Zollinger-Ellison Syndrome. Esomeprazole Is Also Used To Promote the Healing Of Erosive Esophagitis
Mechanism of action:
Esomeprazole works by binding irreversibly to the H+/K+ ATPase in the proton pump. Because the proton pump is the final pathway for the secretion of hydrochloric acid by the parietal cells in the stomach, its inhibition dramatically decreases the secretion of hydrochloric acid into the stomach and alters gastric pH.
PHARMACOKINETICS
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) of 20mg. At repeated once daily dosing with 20mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 20mg.
Effect of Food: The AUC after administration of a single 20mg dose of Esomeprazole is decreased by 43-53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals. Food delays and decreases the absorption of Esomeprazole but this does not significantly change its effect on the intragastric acidity
Distribution:
Esomeprazole is 97% bounded to plasma proteins. Plasma protein binding is constant over the concentration range of 2-20 mol/L. The apparent volume of distribution at a steady state in healthy volunteers is approximately 16L.
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 depends upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining part is dependent on CYP3A4 which forms the sulphone metabolite.
Excretion:
Total plasma clearance is about 17L/h after a single dose and about 9L/h after repeated administration. The plasma elimination half life of Esomeprazole is approximately 1-1.5 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.