{"title":"SARS-CoV-2 Mpro抑制剂[14C] RAY1216在中国健康男性受试者体内的药代动力学和质量平衡特征","authors":"Wang Hu, Jiaxiang Ding, Yunqiu Xie, Tonghao Zhang, Yu Peng, Ying Wang, Xiaoni Wang, Peng Xu, Xiaoli Li, Xuefeng Wang, Heyue Wang, Ning Cheng, Jinmei Zhou, Luning Sun, Huan Zhou, Qi Qi","doi":"10.1177/13596535251377204","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundRAY1216 is an alpha-ketoamide-based peptide inhibitor of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) major protease (M<sup>pro</sup>). This study evaluated the absorption, distribution, metabolism and excretion of [<sup>14</sup>C]-labelled RAY1216 by oral administration.Research design and methodsThis phase Ι study was designed to assess the pharmacokinetics, mass balance and metabolic pathways in 6 healthy Chinese adult men after a single fasting oral administration of 240 mL (containing 400 mg/100 μCi) [<sup>14</sup>C] RAY1216.ResultsRAY1216 absorbed rapidly in the plasma, with a C<sub>max</sub> of 1796.83 ng/mL, t<sub>max</sub> of 1.42 h and t<sub>1/2</sub> of 5.97 h. RAY1216 is mainly excreted through feces and a small amount through urine, indicating that the excretion of RAY1216 occurs through the fecal route, within 96 h after administration, the majority (>90%) of the radioactive substances were excreted 104.17% of the metabolites were identified in urine and fecal samples. The radioactive transformation pathways suggest that RAY1216 has multiple metabolic pathways, including Oxidation-dealkylation, Mono-oxidation, Hydrolysis, and Urea binding. There were no reports of death, serious adverse events (SAEs), or withdrawals related to SAEs.ConclusionThe overall recovery rate data of radioactive substances in the excreta of all 6 subjects indicate that favourable mass balance recovery. The overall safety profile is favourable, and it demonstrates promising potential in mitigating both the duration and severity of COVID-19, and the comprehensive clinical safety and therapeutic effect are significantly superior to those of similar COVID-19 treatment drugs. RAY1216 can be referred to and further verified for the Phase II and Phase III clinical trials for the treatment of COVID-19.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"30 5","pages":"13596535251377204"},"PeriodicalIF":2.3000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic and mass balance characterization of [<sup>14</sup>C] RAY1216, a SARS-CoV-2 M<sup>pro</sup> inhibitor, in healthy Chinese male subjects.\",\"authors\":\"Wang Hu, Jiaxiang Ding, Yunqiu Xie, Tonghao Zhang, Yu Peng, Ying Wang, Xiaoni Wang, Peng Xu, Xiaoli Li, Xuefeng Wang, Heyue Wang, Ning Cheng, Jinmei Zhou, Luning Sun, Huan Zhou, Qi Qi\",\"doi\":\"10.1177/13596535251377204\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundRAY1216 is an alpha-ketoamide-based peptide inhibitor of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) major protease (M<sup>pro</sup>). This study evaluated the absorption, distribution, metabolism and excretion of [<sup>14</sup>C]-labelled RAY1216 by oral administration.Research design and methodsThis phase Ι study was designed to assess the pharmacokinetics, mass balance and metabolic pathways in 6 healthy Chinese adult men after a single fasting oral administration of 240 mL (containing 400 mg/100 μCi) [<sup>14</sup>C] RAY1216.ResultsRAY1216 absorbed rapidly in the plasma, with a C<sub>max</sub> of 1796.83 ng/mL, t<sub>max</sub> of 1.42 h and t<sub>1/2</sub> of 5.97 h. RAY1216 is mainly excreted through feces and a small amount through urine, indicating that the excretion of RAY1216 occurs through the fecal route, within 96 h after administration, the majority (>90%) of the radioactive substances were excreted 104.17% of the metabolites were identified in urine and fecal samples. The radioactive transformation pathways suggest that RAY1216 has multiple metabolic pathways, including Oxidation-dealkylation, Mono-oxidation, Hydrolysis, and Urea binding. There were no reports of death, serious adverse events (SAEs), or withdrawals related to SAEs.ConclusionThe overall recovery rate data of radioactive substances in the excreta of all 6 subjects indicate that favourable mass balance recovery. The overall safety profile is favourable, and it demonstrates promising potential in mitigating both the duration and severity of COVID-19, and the comprehensive clinical safety and therapeutic effect are significantly superior to those of similar COVID-19 treatment drugs. RAY1216 can be referred to and further verified for the Phase II and Phase III clinical trials for the treatment of COVID-19.</p>\",\"PeriodicalId\":8364,\"journal\":{\"name\":\"Antiviral Therapy\",\"volume\":\"30 5\",\"pages\":\"13596535251377204\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antiviral Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/13596535251377204\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/13596535251377204","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/10 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Pharmacokinetic and mass balance characterization of [14C] RAY1216, a SARS-CoV-2 Mpro inhibitor, in healthy Chinese male subjects.
BackgroundRAY1216 is an alpha-ketoamide-based peptide inhibitor of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) major protease (Mpro). This study evaluated the absorption, distribution, metabolism and excretion of [14C]-labelled RAY1216 by oral administration.Research design and methodsThis phase Ι study was designed to assess the pharmacokinetics, mass balance and metabolic pathways in 6 healthy Chinese adult men after a single fasting oral administration of 240 mL (containing 400 mg/100 μCi) [14C] RAY1216.ResultsRAY1216 absorbed rapidly in the plasma, with a Cmax of 1796.83 ng/mL, tmax of 1.42 h and t1/2 of 5.97 h. RAY1216 is mainly excreted through feces and a small amount through urine, indicating that the excretion of RAY1216 occurs through the fecal route, within 96 h after administration, the majority (>90%) of the radioactive substances were excreted 104.17% of the metabolites were identified in urine and fecal samples. The radioactive transformation pathways suggest that RAY1216 has multiple metabolic pathways, including Oxidation-dealkylation, Mono-oxidation, Hydrolysis, and Urea binding. There were no reports of death, serious adverse events (SAEs), or withdrawals related to SAEs.ConclusionThe overall recovery rate data of radioactive substances in the excreta of all 6 subjects indicate that favourable mass balance recovery. The overall safety profile is favourable, and it demonstrates promising potential in mitigating both the duration and severity of COVID-19, and the comprehensive clinical safety and therapeutic effect are significantly superior to those of similar COVID-19 treatment drugs. RAY1216 can be referred to and further verified for the Phase II and Phase III clinical trials for the treatment of COVID-19.
期刊介绍:
Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases.
The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.