A Pilot Study in Humans on the Urinary Tract Excretion of the FimH Inhibitor 1-Deoxymannose.

BACKGROUND

FimH inhibitors are anticipated to serve as preventive therapeutics against urinary tract infections. Consequently, multiple inhibitors-predominantly D-mannose derivatives-have been synthesized, and their binding affinities (determined by dissociation coefficient; K) to FimH have been examined in vitro. Nevertheless, the amounts of most of these synthetic compounds that reach the urinary tract after oral administration in humans have not been investigated. D-mannose (Man) and its analog, 1-Deoxymannose (DM), have already been reported to show K values against FimH. Therefore, this study aimed to estimate the post-oral ingestion of FimH inhibitory potentials of DM and Man in the urinary tract.

METHODS

Six participants were given single 1 g doses of DM and Man in a crossover test. The sample concentrations in urine were measured 8 h after ingestion.

RESULTS

DM levels increased rapidly after oral intake; contrarily, Man was detected in the urine before administration, with no notable increase post-ingestion. The peak concentration ranges of Man and DM in urine were 2.15-22.9 μg/mL and 665-57,804 μg/mL, respectively, which are 66.3-707 and 3600-31,200 times that of K respectively.

CONCLUSIONS

These results indicate that DM as a supplement is an orally active FimH inhibitor in the human urinary tract. Conversely, d-mannose is expected to exert comparatively milder inhibition.