Mitsuboshi Satoru, Yamada Hitoshi, Nagai Kazuhiko, Okajima Hideo
Department of Pharmacy, Kaetsu Hospital.
Department of Internal Medicine, Kaetsu Hospital.
Biol Pharm Bull. 2017;40(9):1463-1467. 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.
为了确定血液透析(HD)患者从非布司他转换为托匹司他后的反应,我们评估了HD患者转换后托匹司他的疗效、耐受性和血清浓度。在这项为期16个月的前瞻性观察性研究中,我们评估了10名接受10mg/d非布司他治疗超过1年的HD患者的血清尿酸(UA)水平、其他实验室数据和血清托匹司他浓度。转换为托匹司他后,基线时和16个月时的耐受性指数之间未观察到统计学差异。所有患者转换后血清UA(达到的血清UA水平≤6mg/dL)在基线时为5.6±1.7mg/dL(60%),6个月时为4.9±0.5mg/dL(100%),16个月时为5.7±0.4mg/dL(50%)(p=0.25)。在基线血清UA水平>6mg/dL的患者中,与基线相比,6个月和16个月时血清UA显著降低。血清托匹司他的最低血清浓度低于定量限(<25ng/mL)。我们的结果表明,从10mg/d非布司他转换为40mg/d托匹司他可能会降低血清UA水平,长期来看其他临床实验室数据无变化。这些效果在血清UA水平高的患者中更常见。此外,托匹司他治疗比非布司他治疗更具成本效益。因此,对于在接受10mg/d非布司他治疗后出现高血清UA水平的HD患者,托匹司他治疗可能是更好的治疗选择。