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 (pH4), 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.