A Single- and Multiple-Dose Study to Characterize the Pharmacokinetics and Safety of Dotinurad in Healthy Chinese Adults.

IF 2.7 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2025-10-19 DOI:10.1007/s40261-025-01496-x

Yun Liu, Qian Chen, Hui Sun, Cuiyuan Cai, Kotomi Kawamura, Rieko Kokan, Maiko Nomoto

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引用次数: 0

Abstract

Background and objectives: Dotinurad is a selective uricosuric drug for patients with gout with hyperuricemia. To our knowledge, this is the first study to evaluate the pharmacokinetics (PK) of dotinurad, following single and multiple oral doses in healthy Chinese adults.

Methods: This single-center, open-label, parallel group, phase 1 study had 3 cohorts: A (1-mg single dose), B (single and multiple doses of 4 mg once daily for 7 days), and C (10-mg single dose). Dotinurad was administered on an empty stomach. Healthy nonsmoking Chinese adults aged 18-45 years with body mass index 19-24 k/m² and weight ≥ 50 kg were enrolled; Cohort B required serum urate ≥ 5.5 mg/dL at screening.

Results: In total, 26 subjects were included. After single oral doses of 1, 4, and 10 mg, mean ± standard deviation (SD) plasma dotinurad concentration reached maximum observed plasma concentration (C_max) of 104 ± 18.5, 365 ± 35.2, and 964 ± 101 ng/mL at 3.00-3.50 h, respectively. The mean ± SD terminal elimination phase half-life was 10.1 ± 1.26, 9.87 ± 1.47, and 10.9 ± 1.53 h for the 1, 4, and 10 mg doses, respectively; both area under the plasma concentration-time curve and C_max increased in a dose-proportional manner across the 1-10-mg dose range. During once-daily doses for 7 days, steady state was reached by the 2nd day after the initiation of multiple dosing, with an average steady-state plasma concentration of 186 ± 31.8 ng/mL, indicating minimal accumulation. Treatment-emergent adverse events (TEAEs) occurred in four subjects (15.4%); all were mild and resolved without treatment. No dose-dependent TEAEs were observed.

Conclusion: Single- and multiple-dose PK of dotinurad in healthy Chinese adults showed rapid absorption, rapid elimination, linear PK, and no accumulation with once-daily dosing. Dotinurad was well-tolerated during the 7-day treatment course.

Trial registration: ClinicalTrials.gov: NCT05278676.

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单剂量和多剂量在中国健康成人体内的药代动力学和安全性研究。

背景和目的：Dotinurad是一种选择性降糖药物，用于治疗痛风合并高尿酸血症患者。据我们所知，这是第一个在中国健康成人中评估单次和多次口服多替努的药代动力学（PK）的研究。方法：这项单中心、开放标签、平行组、1期研究有3个队列：A（单次给药1mg）、B（单次和多次给药4mg，每日1次，共7天）和C（单次给药10mg）。Dotinurad是空腹服用的。入选年龄在18-45岁、身体质量指数19-24 k/m2、体重≥50 kg的健康非吸烟中国成年人；B组筛查时要求血清尿酸≥5.5 mg/dL。结果：共纳入受试者26例。单次口服剂量1、4和10 mg后，在3.00-3.50 h，平均±标准差（SD）血浆多肽尿酸浓度分别达到最大观察血浆浓度（Cmax） 104±18.5、365±35.2和964±101 ng/mL。1、4和10 mg的平均±SD末消除期半衰期分别为10.1±1.26、9.87±1.47和10.9±1.53 h；血浆浓度-时间曲线下面积和Cmax均在1- 10mg剂量范围内呈剂量正比增加。每天一次给药，连续7天，多次给药后第2天达到稳态，平均稳态血药浓度为186±31.8 ng/mL，表明积累最小。4名受试者（15.4%）发生治疗后出现的不良事件（teae）；所有病例均为轻度，无需治疗即可痊愈。未观察到剂量依赖性teae。结论：多替努拉德单次和多次给药在中国健康成人体内具有快速吸收、快速消除、线性PK、每日一次给药无蓄积的特点。在7天的治疗过程中，Dotinurad耐受性良好。试验注册：ClinicalTrials.gov: NCT05278676。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.