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Pharmacology: Pharmacodynamics: Omeprazole, a racemic mixture of two active enantiomers, reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once daily dosing. Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+, K+ - ATPase - the acid pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus.
Pharmacokinetics: Omeprazole is rapidly but variably absorbed following oral administration. Absorption is not affected by food. Omeprazole is acid-labile and pharmacokinetics may vary between the various formulations developed to improve oral bioavailability. The absorption of omeprazole also appears to be dose-dependent; increasing the dosage above 40 mg has been reported to increase the plasma concentrations in a non-linear fashion because of saturable first-pass hepatic metabolism. In addition, bioavailability is higher after long-term administration. Bioavailability of omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with impaired hepatic function, but is not markedly affected in patients with renal impairment. On absorption, omeprazole is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxyomeprazole, and to a small extent by CYP3A4 to form omeprazole sulfone. The metabolites are inactive and are excreted mostly in the urine and to a lesser extent in bile. The elimination half-life from plasma is reported to be about 0.5 to 3 hours. Omeprazole is highly bound (about 95%) to plasma proteins.
