Effect of omeprazole on movement of intravenously administered metronidazole into gastric juice and its significance in treatment of Helicobacter pylori.
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 against H. 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.
Veldhuyzen van Zanten
S J
SJ
Division of Gastroenterology, Faculty of Medicine, Dalhousie University, Victoria General Hospital, Halifax, Nova Scotia, Canada.
Pollak
P T
PT
Kapoor
H
H
Yeung
P K
PK
D000328:Adult; D001693:Biological Transport, Active; D004359:Drug Therapy, Combination; D005750:Gastric Juice / Q000737:chemistry / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use
D008795:Metronidazole; D009853:Omeprazole