Indications
Omeprazole, as detailed in the FDA label, is a proton pump inhibitor (PPI) employed in several therapeutic applications. It is prescribed for the treatment of active duodenal ulcers in adults and is effective in eradicating Helicobacter pylori to mitigate the recurrence risk of duodenal ulcers. It also addresses active benign gastric ulcers in adults and reduces the risk of upper gastrointestinal bleeding in critically ill adult patients. Furthermore, omeprazole is used to manage symptomatic gastroesophageal reflux disease (GERD) in patients aged one year and older, treat and maintain the healing of erosive esophagitis (EE) due to acid-mediated GERD in patients aged one month and above, and addresses pathologic hypersecretory conditions in adults.
Pharmacodynamics
Omeprazole significantly diminishes gastric acid secretion. Following oral administration, the onset of its antisecretory effect occurs within one hour, with peak efficacy achieved approximately two hours post-administration. The acid inhibition effect of omeprazole is maximal after several days of consistent, once-daily dosing. With continuous use, mild serum gastrin elevation is observed during the initial weeks, aligning with decreased acid secretion, without further increases over time. Although increased gastrin levels may elevate serum Chromogranin A (CgA), potentially affecting neuroendocrine tumor diagnostics, no carcinoids or neoplastic conditions have been confirmed in extensive studies involving over 3,000 patients. To date, omeprazole demonstrates no direct systemic impact on the central nervous, cardiovascular, or respiratory systems, and shows no effect on thyroid function or other hormone levels after short-term dosing.
Absorption
Omeprazole delayed-release capsules consist of enteric-coated granules, ensuring that absorption occurs post-gastric passage, protecting the compound from acidic degradation. The absorption of omeprazole is expedited, reaching peak plasma concentrations within 0.5 to 3.5 hours. Its absolute bioavailability is around 30-40% at doses ranging from 20 to 40 mg, affected predominantly by pre-systemic metabolism. Repeated administration slightly increases its bioavailability.
Metabolism
The metabolism of omeprazole predominantly occurs in the liver via the cytochrome P450 (CYP) enzyme system. The CYP2C19 enzyme, which is expressed polymorphically among individuals, plays a central role, converting omeprazole into hydroxyomeprazole, its primary plasma metabolite. Additionally, CYP3A4 contributes to the formation of omeprazole sulfone, further underscoring the complex metabolic pathways involved.
Mechanism of Action
Omeprazole is a member of the substituted benzimidazole class of antisecretory compounds that effectively inhibit gastric acid secretion through selective interference with the H+/K+ ATPase enzyme system. This proton pump inhibitor achieves its effect by forming covalent bonds with cysteine residues on the alpha subunit of the H+/K+ ATPase pump, leading to the suppression of gastric acid production for up to 36 hours. The degree of this antisecretory effect is dose-dependent and effectively reduces both basal and stimulated acid secretion, regardless of the initiating factor.
