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

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES

Antibiotics-Basel Pub Date : 2025-05-13 DOI:10.3390/antibiotics14050498

Hiromi Hayashi, Naoto Miyazaki, Takuya Kawakami, Shusaku Izumi, Kazuhiro Yoshinaga

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引用次数: 0

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; K_D) 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_D 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_D, 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.

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人类尿路排泄FimH抑制剂1-脱氧甘露糖的初步研究。

背景：FimH抑制剂有望作为尿路感染的预防性治疗药物。因此，合成了多种抑制剂，主要是d -甘露糖衍生物，它们的结合亲和力(由解离系数决定；KD)对FimH的影响。然而，大多数这些合成化合物在人类口服后到达尿路的量尚未被调查。据报道，d -甘露糖（Man）及其类似物1-脱氧甘露糖（DM）显示出对FimH的KD值。因此，本研究旨在评估口服后DM和Man在尿路中的FimH抑制电位。方法：6名参与者在交叉试验中给予单剂量1 g的DM和Man。在摄入后8小时测量尿液中的样品浓度。结果：口服后DM水平迅速升高；相反，在给药前尿液中检测到Man，摄入后没有明显增加。尿中Man和DM的峰值浓度范围分别为2.15 ~ 22.9 μg/mL和665 ~ 57,804 μg/mL，分别是KD的66.3 ~ 707倍和3600 ~ 31200倍。结论：这些结果表明，DM作为一种补充剂，在人尿道中是一种口服活性的FimH抑制剂。相反，d-甘露糖的抑制作用相对温和。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.