EFFECT OF OMEPRAZOLE ON THE DISTRIBUTION OF METRONIDAZOLE, AMOXICILLIN, AND CLARITHROMYCIN IN HUMAN GASTRIC-JUICE

Background & Aims: The mechanism by which antimicrobial therapy agains t Helicobacter pylori is enhanced by acid suppression is unknown. The aim of this study was to investigate the effect of omeprazole on gastr ic juice, plasma, and saliva concentrations of metronidazole, amoxicil lin, and clarithromycin. Methods: Single doses of antibiotic were admi nistered intravenously to 24 healthy men (each antibiotic to 8 subject s) while taking placebo or omeprazole. Antibiotic concentrations were measured in gastric juice, plasma, and saliva. The pharmacokinetic par ameters gastric clearance and gastric transfer fraction were calculate d for each antibiotic. Results: In the omeprazole group compared with the placebo group, mean maximum antibiotic gastric juice concentration s (in milligrams per liter) of metronidazole decreased from 33.6 to 8. 3 (P = 0.0001), whereas those of clarithromycin were unchanged, and th ose of amoxicillin increased from 0.13 to 0.68 (P = 0.02). Omeprazole increased salivary concentrations of metronidazole (P = 0.02) but had no effect on clarithromycin concentrations (no amoxicillin was detecta ble in saliva). Conclusions: Omeprazole decreases the intragastric con centrations of metronidazole by reducing acid secretion and increases intragastric concentrations of amoxicillin partly by reducing gastric juice volume. Novel pharmacokinetic parameters have been described tha t provide an insight into the mechanisms underlying drug transfer acro ss the blood-stomach barrier.