Omeprazole: Pharmacology, Pharmacokinetics and Interactions

Omeprazole is a prodrug which is converted to its active form only at the site of action, namely the parietal cell. There it binds irreversibly with H+-K+-ATPase (the gastric proton pump), which causes an effective and long-lasting inhibition of gastric acid secretion. The pharmacokinetic profile of omeprazole is rather complicated, showing concentration-dependent elimination kinetics and an oral bioavailability which increases with the dose and during repeated administration. For the choice of dosage regimens this has minor consequences, in view of the wide therapeutic range of omeprazole and because an almost continuous maximum effect is obtained with once daily oral administration of 20–40 mg. Omeprazole may influence the pharmacokinetics of concurrently administered drugs by an inhibition of their oxidative metabolism. For most drugs studied thus far, the influence is less or even negligible in comparison with the influence of cimetidine, with the exception of diazepam. For every new combination of omeprazole with a drug that has a critical therapeutic range the consequences of a possible interaction should be studied.