ALTERATION OF BILE-ACID METABOLISM BY CIMETIDINE IN HEALTHY HUMANS

Background: To clarify an effect of cimetidine on bile acid metabolism , we evaluated whether an increased deconjugation of bile acids would occur in healthy humans who have received cimetidine, We examined: 1) whether healthy volunteers taking cimetidine would have positive bile acid breath tests because of bacterial overgrowth in the jejunum; 2) w hether the isolated bacteria would exhibit deconjugation ability; and 3) whether a change in gastric pH was related to the bacterial overgro wth. Methods: We evaluated 73 healthy Japanese volunteers; 53 of them received cimetidine and 20 did not. Deconjugation of bile acids was de tected as (CO2)-C-14 specific activity of expired air measured by a bi le acid breath test giving 5 mu Ci of oral glycine-1-C-14 labeled glyc ocholate, Aspiration of jejunal fluids was performed by a double lumen tube with a robber cover on the tip, and deconjugation ability of bac teria was evaluated using thin layer chromatography. Results: Samples of expired breath from the 53 healthy volunteers showed a significant increase in (CO2)-C-14 specific activity after the administration of c imetidine rather than before the administration of cimetidine. Bacteri al overgrowth was found in the jejunal fluid after the administration of cimetidine. The administration of tetracycline to 27 subjects signi ficantly reduced the (CO2)-C-14 specific activity. The following speci es were identified in the jejunal fluid samples obtained from the subj ects: enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uni formis, Eubacterium lentum, E parvum, and Escherichia coli. Except for E coli, all of the bacterial species identified deconjugated bile aci ds. We observed a significant relationship between (CO2)-C-14's specif ic activity and gastric pH before and after administration of cimetidi ne, respectively. Conclusions: Healthy volunteers who received cimetid ine showed an increased deconjugation of bile acid caused by overgrowt h of bacteria in the jejunum, which can deconjugate bile acids. The ba cterial overgrowth is probably associated with a shift to neutral pH i n the gastric juice caused by cimetidine.