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

## TL;DR

This study tested how well 1-Deoxymannose (DM) and D-mannose (Man) reach the urinary tract after being taken orally in humans to prevent urinary tract infections.

## Contribution

The study provides the first human data on the urinary excretion of the FimH inhibitor 1-Deoxymannose after oral administration.

## Key findings

- DM reached high concentrations in urine, much higher than its FimH binding affinity (KD).
- Man was already present in urine before ingestion and showed minimal increase after administration.
- DM's urinary concentration was significantly higher than Man's, suggesting stronger FimH inhibition potential.

## Abstract

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; KD) 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 KD 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 KD, 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.