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An Immature Murine Model of Reversible Unilateral Ureteral Obstruction
Published on: April 4, 2025
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Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel
Tetsuya Taniguchi1, Naoki Ashizawa1, Koji Matsumoto1
1Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
The Journal of Pharmacy and Pharmacology
|November 22, 2015
Summary
A new rat model using topiroxostat effectively evaluates hypouricemic agents by modulating urate formation. This model is sensitive to urate production rates, offering a valuable tool for drug development.
Area of Science:
- Pharmacology
- Biochemistry
- Drug Discovery
Background:
- Gout and hyperuricemia are linked to elevated plasma urate levels.
- Uricosuric agents aim to reduce plasma urate by increasing its excretion.
- Developing reliable preclinical models is crucial for evaluating hypouricemic drug efficacy.
Purpose of the Study:
- To establish a rat model for assessing the hypouricemic effects of uricosuric agents.
- To investigate the influence of urate formation rate on the efficacy of uricosuric drugs.
- To validate the use of topiroxostat in a preclinical model for gout therapeutics.
Main Methods:
- Rats were induced hyperuricemic using potassium oxonate (uricase inhibitor) or hypouricemic using topiroxostat (xanthine oxidoreductase inhibitor).
- Uricosuric agents (FYU-981, F12859, probenecid) were administered to rats under different conditions.
- Co-administration of topiroxostat with inosine (urate precursor) was performed to assess its impact.
Main Results:
- Uricosuric agents showed no hypouricemic effect in potassium oxonate-induced hyperuricemic rats.
- In topiroxostat-treated rats, uricosuric agents significantly reduced plasma urate levels in a dose-dependent manner.
- Co-treatment with inosine abolished the hypouricemic effect of uricosuric agents in topiroxostat-treated rats.
Conclusions:
- The efficacy of uricosuric agents is influenced by the rate of urate formation.
- Topiroxostat-induced reduction in urate formation creates a suitable model for evaluating hypouricemic agents in rats.
- This model offers a valuable platform for preclinical assessment of drugs targeting hyperuricemia.
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