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 determi ne the effect of omeprazole on the movement of metronidazole across th e gastric mucosa into the gastric lumen. Each received a 500-mg intrav enous 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 repea ted following one week of oral omeprazole 20 mg twice daily, Metronida zole concentrations were measured by high-performance liquid chromatog raphy, The results demonstrated that: metronidazole moves rapidly from serum into gastric juice; omeprazole causes a marked reduction in tot al 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 r emain 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 o f the study, indicating that a special transport mechanism may be oper ational. The practical implication of this effect of omeprazole in com bination therapy with metronidazole remains to be established.