Pharmacology: Pharrmacodynamics: 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 the stimulus. All pharmacodynamic effects observed can be explained by the effect of omeprazole on acid secretion.
Pharrmacokinetics: Omeprazole is rapidly but variably absorbed after oral doses. Absorption is not significantly affected by food. Omeprazole is acid-labile and the pharmacokinetics of the various formulations developed to improve oral bioavailability may vary. 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 use. Bioavailability of omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese and in patients with hepatic impairment, but is not markedly affected in patients with renal impairment. On absorption, omeprazole is almost completely metabolised in the liver, primarily by the cytochromeP450 isoenzyme CYP2C19 to form hydroxy-omeprazole 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 about 95% bound to plasma proteins.