Despite their sho half-lives (2 hrs), proton pump inhibitors (PPIs) cause a prolonged Suppression of acid secretion (up to 48 h) because:

The only significant pharmacological action of proton pump inhibitor is dose dependent suppression of gastric acid secretion; without anticholinergic or Hz blocking action. It is a powerful inhibitor of gastric acid: can totally abolish HCl secretion, both resting as well as that stimulated by food or any of the secretagogues, without much effect on pepsin, intrinsic factor, juice volume and gastric motility. Proton pump inhibitors like omeprazole is inactive at neutral pH, but at pH < 5 rearranges to two charged cationic forms (a sulphenic acid and a sulphenamide configurations) that react covalently with SH groups of the H*K*ATPase enzyme and inactivate it irreversibly, especially when two molecules of omeprazole react with one molecule of the enzyme. After diffusing into the parietal cell from blood, it gets concentrated in the acidic pH of the canaliculi because the charged forms generated there are unable to diffuse back. Moreover, it gets tightly bound to the enzyme (Essentials of pharmavology KD Tripathy,6th edition,pg no.631)