Pharmacokinetic and mass balance characterization of [14C] RAY1216, a SARS-CoV-2 Mpro inhibitor, in healthy Chinese male subjects.

IF 2.3 4区 医学 Q4 INFECTIOUS DISEASES
Antiviral Therapy Pub Date : 2025-10-01 Epub Date: 2025-09-10 DOI:10.1177/13596535251377204
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
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引用次数: 0

Abstract

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.

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
dray1216是一种基于α -酮酰胺的严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)主要蛋白酶(Mpro)肽抑制剂。本研究评估了口服[14C]标记的RAY1216的吸收、分布、代谢和排泄。研究设计与方法Ι期研究旨在评估6名健康中国成年男性在单次空腹口服240 mL(含400 mg/100 μCi) [14C] RAY1216后的药代动力学、质量平衡和代谢途径。结果RAY1216在血浆中吸收迅速,Cmax为1796.83 ng/mL, tmax为1.42 h, tmax为5.97 h的1/2。RAY1216主要通过粪便排出,少量通过尿液排出,说明RAY1216是通过粪便途径排出的,给药后96 h内,大部分放射性物质(> - 90%)被排出,尿液和粪便样品中鉴定出代谢产物的104.17%。放射性转化途径表明RAY1216具有多种代谢途径,包括氧化-脱烷基、单氧化、水解和尿素结合。没有死亡、严重不良事件(SAEs)或与SAEs相关的停药的报告。结论6例患者排泄物中放射性物质的总体回收率均显示出良好的物质平衡恢复。整体安全性良好,在缓解COVID-19病程和严重程度方面均显示出良好的潜力,综合临床安全性和治疗效果明显优于同类COVID-19治疗药物。RAY1216可以参考并进一步验证用于治疗COVID-19的II期和III期临床试验。
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
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
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.
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