Metabolic Impact of XOR Inhibitors Use and Discontinuation

Xanthine oxidoreductase (XOR) is the only enzyme responsible for uric acid production and is essential for preventing gout. While XOR inhibitors effectively reduce serum urate levels, they also influence purine salvage and de novo pathways, as well as energy metabolism, raising concerns about metabolic adaptation and rebound effects upon treatment discontinuation. In this review, we outline the fundamental regulatory mechanisms of purine metabolism and summarize the mechanisms of action of XOR inhibitors and their associated metabolic effects with reference to XOR deficiency, type I xanthinuria. Furthermore, we discuss the impact of discontinuing XOR inhibitors and examine their potential for rebound.

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Publication Details

Journal
Gout Urate and Crystal Deposition Disease
Published
2025-06-09
DOI
https://doi.org/10.3390/gucdd3020009
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
0.00

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article

Metabolic Impact of XOR Inhibitors Use and Discontinuation

Kimiyoshi Ichida, Mai Sekine
Gout Urate and Crystal Deposition Disease
Cancer, Hypoxia, and Metabolism
article

Metabolic Impact of XOR Inhibitors Use and Discontinuation

Kimiyoshi Ichida, Mai Sekine
article en

Abstract

Xanthine oxidoreductase (XOR) is the only enzyme responsible for uric acid production and is essential for preventing gout. While XOR inhibitors effectively reduce serum urate levels, they also influence purine salvage and de novo pathways, as well as energy metabolism, raising concerns about metabolic adaptation and rebound effects upon treatment discontinuation. In this review, we outline the fundamental regulatory mechanisms of purine metabolism and summarize the mechanisms of action of XOR inhibitors and their associated metabolic effects with reference to XOR deficiency, type I xanthinuria. Furthermore, we discuss the impact of discontinuing XOR inhibitors and examine their potential for rebound.

Gout Urate and Crystal Deposition DiseaseVol. 3(2)
Nippon Veterinary and Life Science University (JP), Tokyo University of Pharmacy and Life Sciences (JP)
Gout and Uric Acid Foundation, Japan Society for the Promotion of Science
Openalex Percentile: Top 82%
Cancer, Hypoxia, and Metabolism
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