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Pharmacokinetics of oral and intravenous omeprazole in patients with the Zollinger-Ellison syndrome

  • Rakesh Vinayek
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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  • Michael A. Amantea
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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  • Paul N. Maton
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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  • Harold Frucht
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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  • Jerry D. Gardner
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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  • Robert T. Jensen
    Correspondence
    Address requests for reprints to: Robert T. Jensen, M.D., National Institutes of Health, Building 10, Room 9C103, Bethesda, Maryland 20892.
    Affiliations
    Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, and Clinical Department of Pharmacy, Clinical Center, National Institutes of Health, Bethesda, Maryland USA
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      Abstract

      The pharmacokinetics and pharmacodynamics of oral and IV omeprazole after a single dose were studied in 9 patients with the Zollinger-Ellison syndrome to determine whether the increased dose required to control gastric acid hypersecretion could be explained on the basis of altered pharmacokinetics. Each patient was studied both after receiving a single IV bolus of omeprazole (40 mg) and after receiving a single oral dose of omeprazole (80 mg). Intravenous and oral omeprazole doses were administered 1 week apart. Gastric acid secretion and plasma concentrations of omeprazole after drug administration were determined in each patient. The area under the plasma concentration curve, clearance, and volume of distribution after IV omeprazole administration and the area under the plasma concentration curve, peak plasma concentration, and time required to reach the peak after oral omeprazole administration were not different from those reported previously for normal subjects and patients with peptic ulcer disease. Mean (±SEM) bioavailability of oral omeprazole for all patients was 68% ± 16%, which was similar to the bioavailability reported previously for normal subjects. Three patients had a significantly lower bioavailability (20% ± 8%) than the others, and their basal acid outputs were significantly higher than those of the other 7 patients. For all patients there was an inverse correlation between bioavailability and basal acid output (r = 0.76; P < 0.02). The mean (±SEM) elimination half-lives of IV and oral omeprazole were not different (2.3 ± 0.4 vs. 2.4 ± 0.5 hours) but were significantly longer than those reported previously for normal subjects (P < 0.02). The duration of action correlated with the elimination half-life of the drug (r = 0.87; P < 0.003) and area under the plasma concentration curve (r = 0.72; P < 0.03). The mean durations of action of IV and oral omeprazole were not significantly different (34 ± 7.2 vs. 35 ± 6.2 hours). It was concluded that altered pharmacokinetics do not account for the increased drug requirement of omeprazole in patients with the Zollinger-Ellison syndrome. In contrast to a previous study, the oral and IV omeprazole had the same duration of action, suggesting that intermittent bolus administration of parenteral omeprazole will obviate the need for continuous infusion of histamine H2-receptor antagonists in patients requiring parenteral antisecretory drugs. Furthermore, an IV dose every 12 hours controlled acid secretion in all patients, suggesting this as the recommended dose interval in patients requiring parenteral drug therapy.

      Abbreviations:

      Vdss (steady-state volume of distribution), ZES (Zollinger-Ellison syndrome)
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