Study of the mass balance, biotransformation and safety of [14C]SHR8554, a novel μ-opioid receptor injection, in healthy Chinese subjects

• DOI: 10.3389/fphar.2023.1231102
• Publication Date: 2023-09-14T17:25:30Z
• Authors: Rupeng Shi; Yi Chai; Hao Feng; Lijun Xie; Lulu Zhang; Tianqi Zhong; Juan Chen; Peng Yan; Bei Zhu; Jun Zhao; Chen Zhou
• Keywords: Active metabolite

Background: SHR8554 is a novel μ-opioid receptor-biased agonist. It has analgesic effects by selectively activating the G protein-coupled pathway. Additionally, it can weakly activate ß-arrestin-2 pathway, resulting in limited number of side effects, such as gastrointestinal inhibition. Previous studies have shown that good safety and tolerability, but pharmacokinetic characteristics humans not been reported. This study was designed to investigate pharmacokinetics healthy Chinese male subjects. Methods: A single 1 mg/41.3 μCi intravenous dose [14C]SHR8554 administered six Blood, urine faecal samples were collected at continuous time points analyse parent drug levels their metabolites. The total radioactivity blood, plasma, faeces detected using liquid scintillation counter. dynamic changes its metabolite concentration chromatography-tandem mass spectrometry (LC/MS), then analysis. on subjects also observed after injection. Results: recovery 99.68% ± 0.79% 216 h, including 76.22% 1.12% 23.46% 1.36% faeces. Seventeen major metabolites analysed identified. main metabolic pathways human body involve 1) N-dealkylation; 2) O-deethylation; 3) mono-oxidation; 4) glucuronidation, etc. primary mechanism clearance through urinary excretion, primarily forms. safety, no serious adverse observed. Conclusion: showed favourable profiles this study. extensively metabolized body. include N-dealkylation O-deethylation, well mono-oxidation glucuronidation. excretion route urine. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/, identifier CTR20220450.