Mapping the Metabolic Fate of Suzetrigine in Equine and Camel Models: A Step Toward Reliable Antidoping Detection
Abstract
RATIONALE: Effective pain management remains a persistent challenge, with opioids limited by tolerance, dependence, respiratory depression, and misuse. This has created demand for safer, nonaddictive alternatives. Suzetrigine (VX-548, Journavx) is a novel analgesic with promising efficacy, but its potential misuse in competitive racing requires investigation. Limited information is available on its metabolism and detection, emphasizing the need for metabolic characterization to aid antidoping strategies.
METHODS: In vitro metabolism of suzetrigine was evaluated using equine liver microsomes and homogenized camel liver. Metabolic profiling was carried out using high-resolution LC-HRMS. Fragmentation analysis was performed to assign metabolite structures and characterize biotransformation pathways.
RESULTS: Seven phase I metabolites (M1-M7) were identified, primarily via hydroxylation, methylation, demethylation, detrifluoromethylation, and cleavage of the pyridine-2-carboxamide moiety. One phase II metabolite (M8), formed by sulfation of the demethylated metabolite M5, was detected exclusively with camel liver. Metabolite structures were tentatively assigned based on mass fragmentation data, which showed characteristic neutral losses and diagnostic ions. Comparative analysis revealed that both species shared common phase I pathways, but camel liver demonstrated additional conjugation capacity.
CONCLUSION: This study provides the first comprehensive characterization of…
Read the paper
Related studies
- Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min
- De Novo Transcriptome Analysis and Detection of Antimicrobial Peptides of the American Cockroach Periplaneta americana (Linnaeus)
- Molecular Characterization and Expression Profiling of Tomato GRF Transcription Factor Family Genes in Response to Abiotic Stresses and Phytohormones
- Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner
- Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening
- Machine Learning-Based SERS Chemical Space for Two-Way Prediction of Structures and Spectra of Untrained Molecules
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.