Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects.

Abstract

1. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]‐omeprazole was given simultaneously with the first and last oral doses and blood sampling was performed thereafter. In order to study the extent of absorption at minimal acid exposure, a single dose of 20 mg omeprazole was also given as a buffered solution, before and after the treatment with EC granules. 2. Kinetic parameters of omeprazole after the i.v. tracer dose were unchanged on repeated dosing while AUC increased by approximately 40% for the solution and 60% for the EC granules. 3. The increased AUC is caused by an increased systemic availability, which may be explained by a decreased first‐pass elimination during repeated treatment and/or by a reduced degradation of omeprazole in the stomach secondary to the profound decrease in intragastric acidity caused by the drug. 4. The implication of these findings is that the antisecretory effect of therapeutic doses of omeprazole must be studied during repeated administration and not judged from studies using single doses only.

Nonlinear kinetics after high-dose omeprazole caused by saturation of genetically variable CYP2C19

“…The kinetic parameters after multiple omeprazole doses resemble those reported by other authors. 7,12,13 However, a direct comparison is difficult because omeprazole kinetics vary with dose, duration of treatment, and with CYP2C19 phenotype. The threefold increase of AUC following a dose escalation of only 50% from 40 to 60 mg seems to be more pronounced than in studies using lower omeprazole doses.…”

“…The threefold increase of AUC following a dose escalation of only 50% from 40 to 60 mg seems to be more pronounced than in studies using lower omeprazole doses. [7][8][9][10][11][12][13] With respect to metabolite kinetics, a good correlation between elimination parameters of omeprazole and omeprazole sulfone was reported after single doses, 9 This finding could be reproduced.…”

“…2,6 Thus far, omeprazole kinetics were were investigated after treatment with repeated high studied upon single doses of 10 to 80 mg [7][8][9][10][11] Two major primary metabolites, omeprazole sulfone that CYP2C19-dependent plasma clearance of omepra-and 5 -hydroxyomeprazole, are formed by cytochromes zole and omeprazole sulfone was reduced from 19.0 to P450 3A (CYP3A) and 2C19 (CYP2C19), respectively 8.4 L/h (P õ .001) and from 19.8 to 9.2 L/h (P Å .012), (Fig. 1).…”

Influence of acid secretory status on absorption of omeprazole from enteric coated granules.

“…Previous studies with repeated once daily oral administration of omeprazole as EC granules in different doses have shown that the AUC increases during the first 4 days of treatment with no further rise thereafter during continued treatment (Andersson et al, 1990;Muller et al, 1983;Prichard et al, 1985). The increase in AUC has also been shown to be dose-dependent between 10 and 40 mg with a more pronounced increase with higher doses (Andersson et al, 1989).…”

Pharmacokinetics of two formulations of omeprazole administered through a gastrostomy tube in patients with severe neurodevelopmental problems

“…Considerable interindividual variability, particularly in area under the plasma concentration-time curve (AUC) data, has been described before for both intravenous and oral administration of omeprazole in children [6,7] and adults [8,9]. This high variability can be largely attributed to genetic polymorphism of the cytochrome P450 (CYP) isoform CYP2C19 [4,10].…”