Nexium 20 mg

Esomeprazole 20 mg

Pharmacology
Mechanism of Action
S-isomer of omeprazole; PPI; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in blockage of acid secretion

Absorption
Bioavailability: PO: 89-90%; food decreases AUC by 33-53%; take 1 hr before meal
Onset: 1-2 hr (gastric acid inhibition); within 4 wk (GERD)
Duration (multiple dose): Gastric acid inhibition; PO: 17 hr
Peak plasma time: PO: 1-1.6 hr

Distribution
Protein bound: 97%
Vd: 16 L

Metabolism
Liver; extensively metabolized by hepatic P450 enzyme; major metabolic pathway is via CYP2C19; the rest is via CYP3A4
Metabolites: 5-hydroxyesomeprazole (inactive), esomeprazole sulfone (inactive), desmethyl-esomeprazole (activity unknown)
Enzymes inhibited: CYP2C19
Slow metabolizers (3% of Caucasians and African-Americans) are deficient in CPY2C19 enzyme system; plasma concentration can be higher than in persons who have the enzyme

Elimination
Half-life: 1.2-1.5 hr
Total body clearance: 9-16 L/hr
Excretion: Urine (80%); feces (20%)

Pharmacogenomics
Metabolites of esomeprazole lack antisecretory activity
The major part of esomeprazole’s metabolism is dependent on the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites
CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15-20% of Asians lack CYP2C19 and are termed poor metabolizers
At steady state, the ratio of AUC in poor metabolizers to AUC in the rest of the population (extensive metabolizers) is approximately 2
References