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

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 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.

The HOMER Study: The Effect of Increasing the Dose of Metronidazole When Given with Omeprazole and Amoxicillin to Cure Helicobacter pylori Infection

“…Theoretically, one can therefore expect that higher gastric metronidazole levels can be achieved if higher doses of metronidazole are given in combination with PPIs. This study, however, indicates that there is little therapeutic gain when using higher doses of metronidazole, although gastric juice metronidazole levels were not measured [10,11]. It remains to be determined whether a course of treatment longer than a week will overcome the effect of resistance and improve outcome.…”

Gastric Transitional Zones, Areas whereHelicobacterTreatment Fails: Results of a Treatment Trial Using the Sydney Strain Mouse Model

“…The antimicrobial effect of many compounds, including bismuth (33), tetracycline (33), amoxicillin (14), and clarithromycin (10), is reduced under acidic conditions. In contrast, metronidazole has been found to be chemically stable under a wide range of pH values (39).…”

“…The reduced inflammation in mice compared to humans may be one explanation for the high success rate of monotherapy with metronidazole. There are convincing data in the literature that demonstrate that metronidazole can cross the gastric mucosa (13,39). This may improve the success rate with this medication.…”

Pharmacodynamic Effects of Nitroimidazoles Alone and in Combination with Clarithromycin on Helicobacter pylori

“…Metronidazole doses of 500 mg produce mean peak levels in plasma of 11.5 mg/ml, and the metronidazole half-life is 8 h (22). Veldhuyzen van Zanten et al (28) found the metronidazole concentration to be much higher in gastric fluid than in plasma. In the present study, the incubation times and the drug concentrations were chosen according to the half-lives and the clinically achievable concentrations of clarithromycin (5), metronidazole (22), and tinidazole (22).…”