Transfer of clarithromycin to gastric juice is enhanced by omeprazole in Helicobacter pylori-infected individuals.
BACKGROUND
The effects of proton-pump inhibitors and Helicobacter pylori infection on the distribution of drugs employed for the eradication of H. pylori are poorly understood. The aim of this study was to investigate the effects of a 7-day oral administration of 20 mg omeprazole on the distribution of clarithromycin in the gastric juice of individuals with H. pylori infection.


METHODS
Eighteen H. pylori-infected dyspeptic male volunteers without endoscopic lesions were enrolled in a study with an open, randomized, two-period crossover design and a 21-day washout period between phases. Plasma and gastric juice concentrations of clarithromycin in subjects with and without omeprazole pretreatment were measured by means of liquid chromatography coupled to tandem mass spectrometry.


RESULTS
The maximum concentration of clarithromycin (Cmax) and the area under the time-concentration curve from 0 to 2 h (AUC0-2h) were significantly higher in gastric juice than in plasma. Omeprazole treatment further augmented clarithromycin Cmax and AUC0-2h in gastric juice approximately 2-fold (P < 0.05).


CONCLUSIONS
Short-term treatment with omeprazole in H. pylori-positive volunteers increases the amount of clarithromycin transferred to the gastric juice, confirming a synergism between these drugs. Our results suggest the presence of an active transport mechanism for clarithromycin from plasma to the gastric lumen, which is influenced by omeprazole.
Pedrazzoli
J
J
Clinical Pharmacology and Gastroenterology Unit and Dept. of Pathology, São Francisco University Medical School, Bragança Paulista, São Paulo, Brazil. pedrazz@dglnet.com.br
Calafatti
S A
SA
Ortiz
R A
RA
Dias
F E
FE
Deguer
M
M
Mendes
F D
FD
Bento
A P
AP
Pereira
A A
AA
Piovesana
H
H
Ferraz
J G
JG
Lerner
F
F
de Nucci
G
G
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001693:Biological Transport, Active; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004357:Drug Synergism; D005750:Gastric Juice / Q000737:chemistry*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D017291:Clarithromycin; D009853:Omeprazole