Pharmacokinetics of various single intravenous and oral doses of omeprazole

The influence of dose on the kinetics of omeprazole and two of its metabolites, hydroxyomeprazole and the sulphone, has been studied. Ten healthy subjects were given omeprazole 10 and 40 mg iv and 10, 40 and 90 mg orally. No significant dose-related difference in any parameter calculated from the iv experiments was detected. Following the oral solutions, however, there was a dose-dependent increase in systemic availability, probably due to saturable first-pass elimination. The AUC of the sulphone also seemed to increase non-linearly with increasing dose, and that of the hydroxyomeprazole increased in proportion to dose. The slight dose-dependency of the bioavailability of the solution is considered to be of no or limited clinical relevance. Furthermore, since omeprazole is given orally as slowly absorbed enteric coated granules in the dose of 20 mg o.d., the potential for dose-dependent kinetics in clinical practice would be much less than in the present study.