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Digestive Diseases and Sciences

, Volume 41, Issue 9, pp 1845–1852 | Cite as

Effect of omeprazole on movement of intravenously administered metronidazole into gastric juice and its significance in treatment ofHelicobacter pylori

  • Sander J. Veldhuyzen van Zanten
  • P. Timothy Pollak
  • Harsh Kapoor
  • Pollen K. Yeung
Esophageal, Gastric And Duodenal Disorders

Abstract

Four healthy,Helicobacter-negative volunteers were studied to determine the effect of omeprazole on the movement of metronidazole across the gastric mucosa into the gastric lumen. Each received a 500-mg intravenous infusion of metronidazole and repeated serum, and gastric juice samples were obtained concomitantly over an 8-hr study via indwelling intravenous catheter and nasogastric tube. The same protocol was repeated following one week of oral omeprazole 20 mg twice daily. Metronidazole concentrations were measured by high-performance liquid chromatography. The results demonstrated that: metronidazole moves rapidly from serum into gastric juice; omeprazole causes a marked reduction in total metronidazole concentrations in gastric juice, completely accounted for by pH-related shifts in the proportion of ionized metronidazole, but does not alter concentrations of nonionized metronidazole, which remain above the MIC level againstH. pylori; and even under conditions where no pH-related drug trapping occurs (pH>4), concentrations of metronidazole were higher in gastric juice than in serum during most of the study, indicating that a special transport mechanism may be operational. The practical implication of this effect of omeprazole in combination therapy with metronidazole remains to be established.

Key words

Helicobacter pylori metronidazole omeprazole antibiotics combined drug interactions 

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References

  1. 1.
    Chiba N, Rao BV, Rademaker JW, Hunt RH: Meta-analysis of the efficacy of antibiotic therapy in eradicatingHelicobacter pylori. Am J Gastroenterol 87:1716–1727, 1992PubMedGoogle Scholar
  2. 2.
    Graham DY, Klein PD, Opekun AR, Smith KE, Polasani RR, Evans DJ Jr, Evans DG, Alpert LC, Michaletz PA, Yoshimura HH, Adam E:In vivo susceptibility ofCampylobacter pylori. Am J Gastroenterol 84:233–238, 1989PubMedGoogle Scholar
  3. 3.
    Iwahi T, Satoh H, Nakao M, Iwasaki T, Yamazaki T, Kubo K, Tamura T, Imada A: Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity againstHelicobacter pylori. Antimicrob Agents Chemother 35:490–496, 1991PubMedGoogle Scholar
  4. 4.
    McGowan CC, Cover TL, Blaser MJ: The proton pump inhibitor omeprazole inhibits acid survival ofHelicobacter pylori by a urease-independent mechanism. Gastroenterology 107:1573–1578, 1994PubMedGoogle Scholar
  5. 5.
    Bell GD, Powell KU, Burridge SM, Spencer G, Bolton G, Purser K, Brooks S, Prosser S, Harrison G, Gant PW, et al: Short report: Omeprazole plus antibiotic combinations for the eradication of metronidazole-resistantHelicobacter pylori. Aliment Pharmacol Ther 6:751–758, 1992PubMedGoogle Scholar
  6. 6.
    Veldhuyzen van Zanten SJ, Goldie J, Hollingsworth J, Silletti C, Richardson H, Hunt RH: Secretion of intravenously administered antibiotics in gastric juice: Implications for management ofHelicobacter pylori. J Clin Pathol 45:225–227, 1992PubMedGoogle Scholar
  7. 7.
    Best LM, Veldhuyzen van Zanten SJ, Bezanson GS, Haldane DJ, Malatjalian DA: Serological detection ofHelicobacter pylori by a flow microsphere immunofluorescence assay. J Clin Microbiol 30:2311–2317, 1992PubMedGoogle Scholar
  8. 8.
    Kapoor H, Yeung PK, Pollak PT, Veldhuyzen van Zanten SJ: The effect of omeprazole on the secretion of intravenously administered metronidazole (MET) into gastric juice. Am J Gastroenterology 89:1375, 1994 (abstract)Google Scholar
  9. 9.
    Pollak PT: A liquid chromatography assay for the study of serum and gastric juice metronidazole concentrations in the treatment ofHelicobacter pylori. Ther Drug Monit 1966 (in press)Google Scholar
  10. 10.
    Mustofa, Suryawati S, Santoso B: Pharmacokinetics of metronidazole in saliva. Int J Clin Pharmacol Ther Toxicol 29:474–478, 1991PubMedGoogle Scholar
  11. 11.
    Loft S, Dossing M, Poulsen HE, Sonne J, Olesen KL, Simonsen K, Andreasen PB: Influence of dose and route of administration on disposition of metronidazole and its major metabolites. Eur J Clin Pharmacol 30:467–473, 1986PubMedGoogle Scholar
  12. 12.
    Goddard AF, Jessa MJ, Barrett DA, Shaw PN, Idström J-P, Wason C, Wrangstadh M, Spiller RC: Effect of omeprazole on the distribution of antibiotics in gastric juice. Gastroenterology 108(suppl):A102, 1995 (abstract)Google Scholar
  13. 13.
    Lind T, Cederberg C, Ekenved G, Haglund U, Olbe L: Effect of omeprazole—a gastric proton pump inhibitor—on pentagastrin stimulated acid secretion in man. Gut 24:270–276, 1983PubMedGoogle Scholar
  14. 14.
    Howden CW, Forrest JA, Meredith PA, Reid JL: Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man. Br J Clin Pharmacol 20:137–139, 1985PubMedGoogle Scholar
  15. 15.
    Ralph ED: Clinical pharmacokinetics of metronidazole. Clin Pharmacokinet 8:43–62, 1983PubMedGoogle Scholar
  16. 16.
    Lykkegaard Nielsen M, Justesen T: Excretion of metronidazole in human bile. Scand J Gastroenterol 12:1003–1008, 1977PubMedGoogle Scholar
  17. 17.
    Metronidazole.In AHFS Drug Information. GK McEvoy (eds). Bethesda, Maryland, American Hospital Formulary Service, 1995, pp 569–577Google Scholar
  18. 18.
    Logan RP, Gummett PA, Misiewicz JJ, Karim QN, Walker MM, Baron JH: One week eradication regimen forHelicobacter pylori. Lancet 338:1249–1252, 1991PubMedGoogle Scholar
  19. 19.
    Veldhuyzen van Zanten SJO, Hunt RH, Cockerman A, Schep G, Malatjalian D, Matisko A, Jewell D: Adding omeprazole 20 mg once a day to metronidazole/amoxycillin treatment of Hpgastritis: A randomized double blind trial. The importance of metronidazole resistance. Am J Gastroenterol 89:1389, 1994 (abstract)Google Scholar
  20. 20.
    Lind T, Veldhuyzen van Zanten SJO, Unge P, Spiller RC, Bayerdörffer E, O'Morain C, Wrangstadh M, Idström JP: The MACH 1 study: Optimal one-week treatment forH. pylori defined? Gut 37(suppl 1):A4, 1995 (abstract)Google Scholar
  21. 21.
    Bazzoli F, Zagari RM, Fossi P, Pozzato P, Roda E: Efficacy and tolerability of a short term low dose triple therapy for eradication ofHelicobacter pylori. Gastroenterology 104(suppl):A40, 1993 (abstract)Google Scholar
  22. 22.
    McNulty CA, Dent JC, Ford GA, Wilkinson SP: Inhibitory antimicrobial concentrations againstCampylobacter pylori in gastric mucosa. J Antimicrob Chemother 22:729–738, 1988PubMedGoogle Scholar
  23. 23.
    Weil J, Bell GD, Powell K, Morden A, Harrison G, Gant PW, Jones PH, Trowell JE: Omeprazole andHelicobacter pylori: Temporary suppression rather than true eradication. Aliment Pharmacol Ther 5:309–313, 1991PubMedGoogle Scholar
  24. 24.
    Hui WM, Lam SK, Ho J, Lai CL, Lok AS, Ng MM, Lau WY, Branicki FJ: Effect of omeprazole on duodenal ulcer-associated antral gastritis andHelicobacter pylori. Dig Dis Sci 36:577–582, 1991PubMedGoogle Scholar
  25. 25.
    Kuipers EJ, Klinkenberg-Knol EC, Festen HP, Lamers CB, Jansen JB, Snel P, Nelis F, Meuwissen SG: Long-term omeprazole therapy does not affectHelicobacter pylori status in most patients. Scand J Gastroenterol 28:978–980, 1993PubMedGoogle Scholar
  26. 26.
    Bayerdörffer E, Miehlke S, Mannes GA, Sommer A, Hochter W, Weingart J, Heldwein W, Klann H, Simon T, Schmitt W, et al: Double-blind trial of omeprazole and amoxicillin to cureHelicobacter pylori infection in patients with duodenal ulcers. Gastroenterology 108:1412–1417, 1995PubMedGoogle Scholar
  27. 27.
    Hunt RH: pH and Hp—gastric acid secretion andHelicobacter pylori: Implications for ulcer healing and eradication of the organism. Am J Gastroenterol 88:481–483, 1993PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Sander J. Veldhuyzen van Zanten
    • 1
  • P. Timothy Pollak
    • 1
  • Harsh Kapoor
    • 1
  • Pollen K. Yeung
    • 1
  1. 1.From the Divisions of Gastroenterology and General Medicine, Faculty of Medicine and College of PharmacyDalhousie University, Victoria General HospitalHalifaxCanada

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