Omeprazole is a proton pump inhibitor (PPI) that irreversibly inhibits the H+/K+-ATPase. Which statement about PPI pharmacokinetics is most accurate?
- A PPIs are active compounds absorbed from the gut and directly inhibit luminal proton pumps
- B PPIs are reversible, competitive inhibitors with a half-life of 12 hours that directly correlates with acid suppression duration
- C PPIs are acid-labile prodrugs enteric-coated for delivery to the small intestine; they are absorbed systemically, concentrated in parietal cell canaliculi where low pH converts them to sulphenamide active form that covalently binds Cys813/Cys892 of the H+/K+-ATPase alpha subunit ✓
- D PPIs directly block the H2 receptor on parietal cells, reducing histamine-stimulated acid secretion
Explanation
PPIs are benzimidazole prodrugs that are enteric-coated to protect against gastric acid degradation. After small intestinal absorption and hepatic metabolism, they are distributed systemically and selectively accumulated in the acidic microenvironment of parietal cell secretory canaliculi. There, the prodrug is converted to a sulphenamide reactive intermediate that forms a covalent disulphide bond with cysteine residues (Cys813 in the K+-binding domain and Cys892) of the H+/K+-ATPase alpha-subunit, irreversibly inhibiting the pump. Acid suppression outlasts the plasma half-life (~1–2 h) because new pump synthesis (18–24 h) is required for recovery.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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