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Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects

文献类型：期刊论文

作者Yu, Chengyin2,3,4; Qian, Hongjie3,4; Wu, Qingqing3,4; Zou, Yang3,4; Ding, Qicheng3,4; Cai, Yuting3,4; Liang, Liyu2,3,4; Xu, Juncai1; Li, Lei1; Zan, Bin1
刊名CTS-CLINICAL AND TRANSLATIONAL SCIENCE
出版日期2024-02-01
卷号17期号:2页码:10
ISSN号1752-8054
DOI10.1111/cts.13718
通讯作者Liu, Yun(yliu@shxh-centerlab.com)
英文摘要This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX-081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug-resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600 mg, N = 52) and a multiple ascending dose (MAD) arm (200 to 400 mg, N = 30). The influence of food was evaluated using a 400 mg dose within an SAD cohort. Plasma concentrations of WX-081 and M3 (main metabolite of WX-081) were analyzed using a validated liquid-chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT0-t), terminal half-life, and clearance of WX-081 ranged from 18.87 to 52.8 h, 31.39 to 236.57 h, and 6.4 to 80.34 L/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC(0-t)) of WX-081 showed dose-proportional increases in the SAD arm. The disparity between fasted and fed states of WX-081 was significant (p < 0.05), with fed dosing resulting in a 984.07% higher AUC(0-t) and 961.55% higher maximum plasma concentration. In both the SAD and MAD arms, one case each exhibited a 1 degree atrioventricular block. No QTc elongation was observed, and adverse events were not dose-dependent. Favorable exposure, tolerability, safety, and an extended MRT0-t suggest that WX-081 holds promise as a phase II development candidate for drug-resistant TB treatment.
WOS关键词BEDAQUILINE ; TUBERCULOSIS ; DRUGS
资助项目Shanghai Jiatan Pharmaceutical Technology Co., Ltd.
WOS研究方向Research & Experimental Medicine
语种英语
出版者WILEY
WOS记录号WOS:001154817600001
源URL[http://119.78.100.183/handle/2S10ELR8/309066]  
专题中国科学院上海药物研究所
通讯作者Liu, Yun
作者单位1.Shanghai Jiatan Pharmaceut Technol Co Ltd, Guangzhou JOYO Pharm, Shanghai, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Fudan Univ, Shanghai Xuhui Cent Hosp, Zhongshan Xuhui Hosp, Cent Lab, Shanghai, Peoples R China
4.Shanghai Engn Res Ctr Phase I Clin Res & Qual Cons, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Chengyin,Qian, Hongjie,Wu, Qingqing,et al. Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects[J]. CTS-CLINICAL AND TRANSLATIONAL SCIENCE,2024,17(2):10.
APA Yu, Chengyin.,Qian, Hongjie.,Wu, Qingqing.,Zou, Yang.,Ding, Qicheng.,...&Liu, Yun.(2024).Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects.CTS-CLINICAL AND TRANSLATIONAL SCIENCE,17(2),10.
MLA Yu, Chengyin,et al."Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects".CTS-CLINICAL AND TRANSLATIONAL SCIENCE 17.2(2024):10.

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来源：上海药物研究所

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