{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:28:10Z","timestamp":1786429690216,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background and Objective<\/jats:title>\n Cap-dependent endonuclease (CEN) inhibitors are a promising novel class of antiviral agents for influenza treatment. This phase I study aimed to evaluate the mass balance, excretion pathways, and pharmacokinetics of pixavir marboxil (TG-1000), a novel CEN inhibitor prodrug, in healthy humans.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Six healthy Chinese male participants received a single oral dose of 40\u00a0mg (100\u00a0\u03bcCi) [\n 14<\/jats:sup>\n C]pixavir marboxil. Blood, urine, and fecal samples were collected at predefined intervals up to 384\u00a0h post-dose. Total radioactivity was determined using oxidative combustion and liquid scintillation counting. Pharmacokinetic parameters were calculated using non-compartmental analysis, and metabolite profiling was conducted using high-performance liquid chromatography coupled with radiochemical detection and high-resolution mass spectrometry.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Intact pixavir marboxil was undetectable in plasma. Systemic exposure primarily consisted of its active metabolite, pixavir (TG-0527), and a subsequent glucuronide conjugate, TG-0600771. The geometric mean areas under the curve (\n \n \n \n \n \n A<\/mml:mi>\n U<\/mml:mi>\n C<\/mml:mi>\n <\/mml:mrow>\n \n 0<\/mml:mn>\n \u2212<\/mml:mo>\n \u221e<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ) for total radioactivity, pixavir, and TG-0600771 in six participants were 4,220\u00a0hng Eq.\/mL, 2,490\u00a0hng\/mL, and 981\u00a0hng\/mL, respectively. The administered radioactive dose demonstrated a mean cumulative recovery of 91.29%, with 85.62% recovered in feces and 5.68% in urine. Metabolite profiling identified pixavir and TG-0600771 as the major metabolites, with no major cytochrome P450 (CYP)-mediated oxidative metabolites observed in plasma. The single dose of [\n 14<\/jats:sup>\n C]pixavir marboxil was safe and well-tolerated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Pixavir marboxil exhibits a favorable pharmacokinetic profile characterized by rapid systemic conversion to its active metabolite, CYP-independent metabolism, and predominantly non-renal clearance. These favorable pharmacokinetic characteristics support a well-characterized disposition profile with limited reliance on CYP-mediated metabolism and renal excretion of active pixavir.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n This study was registered with Drug Clinical Trial Registration and Information Disclosure Platform, National Medical Products Administration (NMPA), number CTR20231822 (\n http:\/\/www.chinadrugtrials.org.cn\/<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1905373","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:38:09Z","timestamp":1786426689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass balance, excretion, and pharmacokinetics of a single oral dose of [14C]pixavir marboxil in healthy Chinese male participants"],"prefix":"10.3389","volume":"17","author":[{"given":"Chunyang","family":"Zhao","sequence":"first","affiliation":[{"name":"Drug Clinical Trial Center, Shanghai Xuhui Central Hospital\/Xuhui Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Joincare Pharmaceutical Group Industry Co., Ltd.","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Shanghai Xuhui Central Hospital\/Xuhui Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"TaiGen Biotechnology Co., Ltd.","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"TaiGen Biotechnology Co., Ltd.","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Shanghai Xuhui Central Hospital\/Xuhui Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Qian","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center, Shanghai Xuhui Central 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