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Goddard, A.F. et al.

Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice.

BACKGROUND & AIMS: The mechanism by which antimicrobial therapy against Helicobacter pylori is enhanced by acid suppression is unknown. The aim of this study was to investigate the effect of omeprazole on gastric juice, plasma, and saliva concentrations of metronidazole, amoxicillin, and clarithromycin. METHODS: Single doses of antibiotic were administered intravenously to 24 healthy men (each antibiotic to 8 subjects) while taking placebo or omeprazole. Antibiotic concentrations were measured in gastric juice, plasma, and saliva. The pharmacokinetic parameters gastric clearance and gastric transfer fraction were calculated for each antibiotic. RESULTS: In the omeprazole group compared with the placebo group, mean maximum antibiotic gastric juice concentrations (in milligram per liter) of metronidazole decreased from 33.6 to 8.3 (P = 0.0001), whereas those of clarithromycin were unchanged, and those 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 detectable in saliva). CONCLUSIONS: Omeprazole decreases the intragastric concentrations of metronidazole by reducing acid secretion and increases intragastric concentrations of amoxicillin partly by reducing gastric juice volume. Novel pharmacokinetic parameters have been described that provide an insight into the mechanisms underlying drug transfer across the blood-stomach barrier.[1]

References

Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice. Goddard, A.F., Jessa, M.J., Barrett, D.A., Shaw, P.N., Idström, J.P., Cederberg, C., Spiller, R.C. Gastroenterology (1996) [Pubmed]

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