Omeprazole: Pharmacokinetics and Metabolism in Man

Abstract

Omeprazole is acid labile and, therefore, has to be protected from exposure to the acidic gastric juice when given orally. Following a single oral dose of buffered suspension, omeprazole is rapidly absorbed with peak plasma concentrations within 0.5 hours. The volume of distribution is 0.3 litres/kg corresponding to the volume of extracellular water. In contrast to the long duration of antisecretory action, omeprazole is rapidly eliminated from plasma. The half-life is less than 1 hour, and omeprazole is almost entirely cleared from plasma within 3-4 hours. Omeprazole is completely metabolized in the liver. The two major plasma metabolites are the sulphone and hydroxyomeprazole, neither of which contributes to the antisecretory activity. About 80% of a given dose is excreted in the urine, and the remainder via the bile. The absorption of the coated granule formulation dispensed in hard gelatine capsules is slower, with peak concentrations 1-3 hours after dose. Bioavailability after a single dose is 35% and increases during repeated once-daily dosing to 60%. Omeprazole can potentially interact with the hepatic microsomal cytochrome P-450 enzymes. Studies show that the clearance of both diazepam and phenytoin are decreased and their terminal half-lives are increased during concomitant omeprazole treatment, both interactions being attributable to inhibition of hepatic metabolism. No interaction with propranolol or theophylline has been noted.