Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers

Background: Triple therapy including two antibiotics and a proton pump inhi bitor is a rational approach to the treatment of Helicobacter pylori induce d peptic ulcer disease. The interaction of antimicrobial therapy and acid s uppression is not yet well elucidated. Aims: To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volun teers. Methods: In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy voluntee rs over 6 days. Blood plasma levels of the drugs were measured. In addition , roxithromycin concentrations were also determined in gastric juice and ga stric tissue obtained during endoscopy. Results: The proton pump inhibitors and roxithromycin did not alter the blo od plasma pharmacokinetics of each other. When compared to roxithromycin ad ministered alone, its combination with a proton pump inhibitor significantl y increased the roxithromycin concentrations in gastric juice (3.0-5.0 mu g /mL vs. 0.3-0.4 mu g/mL) and gastric tissue (antrum: 3.8-4.0 vs. 2.8 mu g/g , fundus: 5.9-7.4 vs. 4.2-4.4 mu g/g). Conclusions: Proton pump inhibitors and roxithromycin do not alter the syst emic bioavailability of each other. However, proton pump inhibitors increas e the local concentration of roxithromycin in the stomach which may contrib ute to the clinically proven synergic beneficial action in eradication ther apy of H. pylori.