{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T15:08:10Z","timestamp":1794409690388,"version":"4.9.0"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX\u2010081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug\u2010resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600\u2009mg, <jats:italic>N<\/jats:italic>\u2009=\u200952) and a multiple ascending dose (MAD) arm (200 to 400\u2009mg, <jats:italic>N<\/jats:italic>\u2009=\u200930). The influence of food was evaluated using a 400\u2009mg dose within an SAD cohort. Plasma concentrations of WX\u2010081 and M3 (main metabolite of WX\u2010081) were analyzed using a validated liquid\u2010chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT<jats:sub>0\u2010t<\/jats:sub>), terminal half\u2010life, and clearance of WX\u2010081 ranged from 18.87 to 52.8\u2009h, 31.39 to 236.57\u2009h, and 6.4 to 80.34\u2009L\/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC<jats:sub>0\u2010t<\/jats:sub>) of WX\u2010081 showed dose\u2010proportional increases in the SAD arm. The disparity between fasted and fed states of WX\u2010081 was significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), with fed dosing resulting in a 984.07% higher AUC<jats:sub>0\u2010t<\/jats:sub> 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\u2010dependent. Favorable exposure, tolerability, safety, and an extended MRT<jats:sub>0\u2010t<\/jats:sub> suggest that WX\u2010081 holds promise as a phase II development candidate for drug\u2010resistant TB treatment.<\/jats:p>","DOI":"10.1111\/cts.13718","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T10:23:00Z","timestamp":1706696580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Safety, pharmacokinetics, and food effect of sudapyridine (WX\u2010081), a novel anti\u2010tuberculosis candidate in healthy Chinese subjects"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-0140","authenticated-orcid":false,"given":"Chengyin","family":"Yu","sequence":"first","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"},{"name":"Central Laboratory Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui 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