The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Hemodial Int. 2018 Jul;22(3):388-393. doi: 10.1111/hdi.12620. Epub 2017 Dec 11.

Abstract

Introduction: Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients.

Methods: Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential.

Findings: Twenty-five of twenty-seven patients completed study. The mean serum uric acid levels in the topiroxostat-treated arm was significantly lower than it in the allopurinol-treated arm time-dependently (P < 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat-arm (*P = 0.0035), but not in allopurinol-arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation-reduction potential, and capacity oxidation-reduction potential between pre and post treatment of both drugs.

Discussion: It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.

Keywords: Oxidative stress; cross over; uric acid lowering.

MeSH terms

  • Aged
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Hyperuricemia / drug therapy*
  • Male
  • Middle Aged
  • Nitriles / pharmacology
  • Nitriles / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Renal Dialysis / methods*
  • Treatment Outcome
  • Uric Acid / blood*

Substances

  • Enzyme Inhibitors
  • Nitriles
  • Pyridines
  • FYX-051
  • Uric Acid