PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS BETWEEN OMEPRAZOLE AND AMOXICILLIN IN HELICOBACTER PYLORI-POSITIVE HEALTHY-SUBJECTS

Background: Omeprazole with amoxycillin has been used to treat Helicob acter pylori infection. It was speculated that omeprazole-induced hypo acidity enhances the antibacterial activity of amoxycillin. Limited in formation exists about intragastric pH and bioavailability of amoxycil lin during combination therapy. No data are available about possible e ffects of the antibiotic on the pharmacokinetics and pharmacodynamics of omeprazole. Methods: The study was performed in a three-way cross-o ver double-blind design. After a run-in period on placebo with a basel ine intragastric pH-metry, 24 H. pylori-positive healthy subjects were randomly dosed with amoxycillin 750 mg b.d. + placebo, amoxycillin 75 0 mg b.d. + omeprazole 40 mg b.d. and omeprazole 40 mg b.d. + placebo for 5 days. On the last day of each regimen intragastric pH-metries we re performed, and blood samples taken for omeprazole and amoxycillin s erum profiles. Results: Amoxycillin monotherapy had no acid-inhibiting effect. Median pH during combined dosing was significantly lower, com pared to omeprazole monotherapy (P < 0.01). Mean serum concentrations of omeprazole and amoxycillin given alone or in combination were not d ifferent. Conclusions: High-dose omeprazole does not alter the pharmac okinetics of amoxycillin. The significantly lower intragastric pH duri ng combination therapy might be due to the H. pylori-suppressive effec t of this treatment.