Comparison of Clinical Advantage between Topiroxostat and Febuxostat in Hemodialysis Patients

• Published in: Biological & pharmaceutical bulletin Vol. 40; no. 9; pp. 1463 - 1467
• Main Authors: Mitsuboshi, Satoru, Yamada, Hitoshi, Nagai, Kazuhiko, Okajima, Hideo
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Adult; Aged; febuxostat; Febuxostat - adverse effects; Febuxostat - pharmacokinetics; Febuxostat - therapeutic use; Female; Follow-Up Studies; Hemodialysis; Humans; Hyperuricemia - drug therapy; Laboratories; Male; Middle Aged; Nitriles - adverse effects; Nitriles - pharmacokinetics; Nitriles - therapeutic use; Prospective Studies; Pyridines - adverse effects; Pyridines - pharmacokinetics; Pyridines - therapeutic use; Renal Dialysis; serum concentration; serum uric acid level; topiroxostat; Uric acid; Uric Acid - blood; Uricosuric Agents - adverse effects; Uricosuric Agents - pharmacokinetics; Uricosuric Agents - therapeutic use; topiroxostat; hemodialysis; serum concentration; febuxostat; serum uric acid level
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00284

To determine the response of hemodialysis (HD) patients to topiroxostat after a switch from febuxostat, we evaluated the efficacy, tolerability, and serum concentration of topiroxostat in HD patients after the switch. In this 16-month prospective observational study, we assessed the serum uric acid (UA) levels, other laboratory data, and serum topiroxostat concentrations of 10 HD patients who had been receiving febuxostat at a dose of 10 mg/d for over 1 year. No statistical difference was observed between the tolerability index at baseline and 16 months after the switch to topiroxostat. Serum UA after the switch in all patients (attained serum UA levels of ≤6 mg/dL) was 5.6±1.7 mg/dL (60%) at baseline, 4.9±0.5 mg/dL (100%) at 6 months and 5.7±0.4 mg/dL (50%) at 16 months (p=0.25), respectively. In patients with baseline serum UA levels >6 mg/dL, serum UA was significantly reduced at 6 and 16 months compared with baseline. Minimum serum concentrations of serum topiroxostat were lower than the limit of quantification (<25 ng/mL). Our results indicate that a switch from febuxostat 10 mg/d to topiroxostat 40 mg/d might reduce serum UA levels, with no change in other clinical laboratory data over the long term. These effects were more frequent in patients with high serum UA levels. Furthermore, topiroxostat therapy was more cost effective than febuxostat therapy. Thus, topiroxostat therapy could be a better treatment option for HD patients who develop high serum UA levels after febuxostat 10 mg/d administration.