title: Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel xanthine oxidoreductase inhibitor.
abstract: OBJECTIVE
  The aim of this study was to establish the rat model for evaluating hypouricemic effects by some uricosuric agents.
  
  
  METHODS
  Rats were made hyperuricemic by subcutaneous administration of potassium oxonate, a uricase inhibitor, or made hypouricemic by oral administration of topiroxostat, a xanthine oxidoreductase inhibitor. Furthermore, rats were co-treated with topiroxostat and inosine, a urate precursor. In each condition, hypouricemic effects by uricosuric agents were examined.
  
  
  RESULTS
  In potassium oxonate-treated rats, treatment with uricosuric agents such as FYU-981, F12859 and probenecid showed no hypouricemic effect. On the other hand, in topiroxostat-treated rats, uricosuric agents remarkably lowered plasma urate level compared with topiroxostat treatment alone, with a dose dependency of 30 and 100 mg/kg for FYU-981 and F12859 each. The decrease in the plasma urate level observed in the topiroxostat-treated rats disappeared by further co-treatment with inosine.
  
  
  CONCLUSIONS
  Effects of uricosuric agents on the plasma urate level in rats were sensitive to the rate of urate formation. Induction of slower urate formation by topiroxostat provides valuable model for evaluation of hypouricemic effects by uricosuric agents in rats.
authors.affiliation: Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ashizawa
authors.affiliation: Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwanaga
authors.affiliation: Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Nishi-ku, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Saitoh
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010094:Oxonic Acid / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014503:Urate Oxidase / Q000378:metabolism; D014527:Uric Acid / Q000097:blood*; D014528:Uricosuric Agents / Q000494:pharmacology*; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009570:Nitriles; D011725:Pyridines; D014528:Uricosuric Agents; C504882:FYX-051; D014527:Uric Acid; C489337:potassium oxonate; D007288:Inosine; D010094:Oxonic Acid; D014968:Xanthine Dehydrogenase; D014503:Urate Oxidase; D011339:Probenecid
keywords: probenecid; topiroxostat; urate; uricosuric agent; xanthine oxidoreductase inhibitor