Hosoya Tatsuo, Sasaki Tomomitsu, Ohashi Tetsuo
Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, Tokyo, Japan.
Development Department, Medical R&D Division, Fuji Yakuhin Co., Ltd., 4-383, Sakuragi-cho, Omiya-ku, Saitama-shi, Saitama, 330-9508, Japan.
Clin Rheumatol. 2017 Mar;36(3):649-656. doi: 10.1007/s10067-016-3474-8. Epub 2016 Nov 10.
Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose-response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose-response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be -44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose-response relationship in Japanese hyperuricemic patients with or without gout.
托匹司他是一种选择性黄嘌呤氧化还原酶抑制剂，在日本用于治疗伴有或不伴有痛风的高尿酸血症患者。关于托匹司他降低血清尿酸水平的有效性，已对剂量反应关系进行了评估；然而，仍有待验证。对伴有或不伴有痛风的日本高尿酸血症患者进行了一项托匹司他的随机、多中心、双盲研究。在为期16周的研究中，157例伴有或不伴有痛风的日本高尿酸血症患者被随机分配接受安慰剂、120或160mg/天的托匹司他，或200mg/天的别嘌醇。本研究的主要终点是确定给药结束时血清尿酸水平相对于基线水平的降低率。安慰剂以及120mg/天和160mg/天的托匹司他组均证实了剂量反应关系（关于血清尿酸水平的降低）。此外，在给药结束时，托匹司他160mg/天组的血清尿酸水平降低率为-44.8%。所有组，包括别嘌醇组，不良事件的发生率均未观察到显著差异。在伴有或不伴有痛风的日本高尿酸血症患者中，发现托匹司他的血清尿酸降低作用具有剂量反应关系。
