Transfer of metronidazole to gastric juice: impact of Helicobacter pylori infection and omeprazole.
BACKGROUND
The effects of Helicobacter pylori infection associated with inhibition of gastric acid secretion on the distribution of medications used for H. pylori eradication are poorly understood. The aim of this study was to investigate the effects of a 7-day administration of 20 mg omeprazole on the transfer of metronidazole from plasma to the gastric juice of individuals with and without H. pylori infection.


METHODS
Fourteen H. pylori-positive and 14 H. pylori-negative male volunteers were enrolled in a study with an open, randomized, two-period crossover design with a 21-day washout period between phases. Plasma, salivary, and gastric juice concentrations of metronidazole in subjects with and without omeprazole treatment were measured with reversed-phase high-performance liquid chromatography/liquid chromatography.


RESULTS
Metronidazole peak concentration (Cmax) was similar in plasma and saliva and was approximately threefold higher in gastric juice in all groups. Omeprazole treatment increased gastric pH and did not affect metronidazole Cmax or the time required for this to be reached (tmax) in plasma, saliva, or gastric juice. However, omeprazole significantly reduced metronidazole transfer from plasma to gastric juice in H. pylori-positive but not H. pylori-negative subjects, as shown by statistical analysis of AUC(0-2 h).


CONCLUSIONS
Short-term treatment with omeprazole in H. pylori- positive volunteers reduces the amount of metronidazole transferred from plasma to gastric juice. This seems to occur in a pH-independent form.
Calafatti
S A
SA
Dept. of Pathology, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
dos Santos
A
A
da Silva
C M
CM
Deguer
M
M
Carvalho
A F
AF
Mendes
F D
FD
Ferraz
J G
JG
Bento
A P
AP
Pereira
A A
AA
Piovesana
H
H
de Nucci
G
G
Lerner
F
F
Pedrazzoli
J
J
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005750:Gastric Juice / Q000737:chemistry*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012463:Saliva / Q000737:chemistry
D000900:Anti-Bacterial Agents; D008795:Metronidazole