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

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

  • Antivir Ther. 2025 Oct;30(5):13596535251377204. doi: 10.1177/13596535251377204.
Wang Hu 1 2,  Jiaxiang Ding 2 3,  Yunqiu Xie 1 2,  Tonghao Zhang 1 2,  Yu Peng 1 2,  Ying Wang 1 2,  Xiaoni Wang 1 2,  Peng Xu 1 2,  Xiaoli Li 1 2,  Xuefeng Wang 1 2,  Heyue Wang 1 2,  Ning Cheng 1 2,  Jinmei Zhou 1 2,  Luning Sun 2 4,  Huan Zhou 1 2 3,  Qi Qi 2 5
Affiliations

Affiliations

  • 1 Clinical Trial Research Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
  • 2 Key Laboratory of Innovative Pharmaceutical Research and Clinical Evaluation Jointly Constructed by Anhui, Bengbu, China.
  • 3 Clinical Research Hospital, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 4 Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 5 School of Basic Medicine, Bengbu Medical University, Bengbu, China.
PMID: 40926690 DOI: 10.1177/13596535251377204
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.

Keywords

ADME; COVID-19; Mass balance; RAY1216; SARS-CoV-2; Safety.

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