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The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis
Authors:Yume Nagaoka  Yoshiko Tanaka  Hiroshi Yoshimoto  Rie Suzuki  Kakei Ryu  Mio Ueda  Minako Akiyama  Miho Nagai  Yoshitaka Miyaoka  Eiichiro Kanda  Shinnichi Iwai  Michio Nagaoka  Yoshihiko Kanno
Affiliation:1. Department of Nephrology, Tokyo Medical University, Tokyo, Japan;2. Nagaoka Hospital, Kaminoyama, Japan;3. Shinjuku Ishikawa Clinic, Tokyo, Japan;4. Department of Nephrology, Tokyo Yamate Medical Center, Tokyo, Japan;5. Department of Healthcare and Regulatory Sciences, Showa University School of Pharmacy, Tokyo, Japan;6. Department of Nephrology, Tokyo Kyosai Hospital, Tokyo, Japan
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  uric acid lowering  cross over
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