EFFECT OF OMEPRAZOLE ON MOVEMENT OF INTRAVENOUSLY ADMINISTERED METRONIDAZOLE INTO GASTRIC-JUICE AND ITS SIGNIFICANCE IN TREATMENT OF HELICOBACTER-PYLORI
Sjv. Vanzanten et al., EFFECT OF OMEPRAZOLE ON MOVEMENT OF INTRAVENOUSLY ADMINISTERED METRONIDAZOLE INTO GASTRIC-JUICE AND ITS SIGNIFICANCE IN TREATMENT OF HELICOBACTER-PYLORI, Digestive diseases and sciences, 41(9), 1996, pp. 1845-1852
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.