Pharmacokinetics and Metabolism of Omeprazole in Man

Abstract

Four studies of the pharmacokinetics and metabolism of omeprazole are briefly discussed. Two of these were carried out in young healthy subjects and indicated that about 54% of an oral dose is available to the systemic circulation. The distribution of omeprazole after an intravenous dose was consistent with localization of a major fraction of the drug in the extracellular water, with about 25% restricted to the blood. Omeprazole was rapidly cleared and possessed the characteristics of a high clearance drug; insignificant amounts of ¹⁴C-omeprazole were excreted by the kidneys, though metabolites were excreted very rapidly. Six different metabolites were reported, the major one being hydroxy-omeprazole. Increasing the intravenous dose of omeprazole from 10 mg to 40 mg had no significant effect on the pharmacokinetic parameters determined. A study in patients with impaired renal function showed that this had little effect on the kinetics of omeprazole, though excretion of metabolites was significantly affected. A study of elderly healthy subjects suggested that the disposition characteristics of omeprazole are affected to some extent by age; further studies are needed to elucidate the clinical implications. Omeprazole has been reported to prolong the half-life of diazepam which may be due to inhibition of the demethylation of diazepam. The interaction of omeprazole with the kinetics of aminopyrine and antipyrine was much less pronounced.