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Effects of Lansoprazole and Amoxicillin on Uptake of [14C]Clarithromycin into Gastric Tissue in Rats

ABSTRACT Triple therapy consisting of clarithromycin (CLR), lansoprazole (LPZ), and amoxicillin (AMZ) is effective as eradication therapy for patients with peptic ulcer disease and Helicobacter pylori infection. We evaluated the effects of LPZ and AMZ on the uptake of [14C]CLR into the gastric tissue of rats. After administration of [14C]CLR alone or in combination with LPZ and AMZ, the distributions of [14C]CLR in the main organs and gastrointestinal tissues were compared. LPZ and AMZ had no effect on the distribution of [14C]CLR in any tissue except gastric tissue. The concentration of radioactivity in gastric tissue was several times higher when [14C]CLR was administered orally together with LPZ than when it was administered alone. The gastric emptying of [14C]CLR became smaller in the case of the coadministration of LPZ. AMZ had no apparent influence on the disposition of [14C]CLR. After the intravenous administration of [14C]CLR, no effects of drug coadministration were evident. In vitro uptake of [14C]CLR into gastric tissue was enhanced in the case of a high-pH environment. The uptake was not influenced by the concurrent presence of LPZ and AMZ. These results suggest that the penetration of [14C]CLR possibly depends on elevated gastric pH, as gastric acid secretion was inhibited by LPZ, and this may be a primary factor in explaining why the concentration of [14C]CLR at the target site, gastric tissue, was enhanced by the coadministration of LPZ.