Omeprazole: Mechanism of Action
Omeprazole is a proton pump inhibitor (PPI) that reduces gastric acid production and is used to treat acid reflux, GERD, and peptic ulcers.
Omeprazole is the prototypical PPI with potent irreversible proton pump inhibition, but efficacy varies significantly with CYP2C19 pharmacogenomics.
How It Works
Omeprazole is a racemic benzimidazole sulphoxide prodrug absorbed in the small intestine and concentrated in acidic parietal cell canaliculi, where acid-catalysed conversion to a reactive sulfenamide occurs. This sulfenamide forms stable disulfide bonds with Cys813 and Cys892 on H⁺/K⁺-ATPase, causing irreversible inhibition. The S-enantiomer (esomeprazole) has a longer plasma half-life and less CYP2C19-dependent clearance. Omeprazole shows the greatest CYP2C19 variability among PPIs — poor metabolisers (~3% Caucasians, ~15–20% Asians) achieve 3–5× higher AUC than extensive metabolisers, explaining variable acid suppression across populations.
Receptor / Target Profile
- •H⁺/K⁺-ATPase Cys813 and Cys892 — covalent irreversible inhibition
- •CYP2C19 — primary metabolism (extensive vs poor metaboliser variability explains 3–10× dose–response differences)
- •CYP3A4 — secondary metabolism
- •CYP2C19 (as inhibitor) — omeprazole moderately inhibits CYP2C19; clinically relevant for clopidogrel interaction
Pharmacokinetics
Onset of Action
Gastric pH rises within 1 hour; maximal effect at steady state after 4–5 days
Half-Life (t½)
1–1.5 hours plasma; pharmacodynamic effect persists 24+ hours
Enteric-coated capsule absorbed at pH >5.5 in small intestine. 95% protein-bound. Short half-life but prolonged pharmacodynamic effect. Take 30–60 minutes before first meal for optimal timing of pump inhibition during active acid secretion.
Conditions Treated with Omeprazole
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