Identification of Metabolites for the Novel 5α-Reductase Inhibitor Epristeride In Vitro and Its Potential Impact on Doping Testing

The study investigates the metabolic pathways of epristeride, a novel noncompetitive inhibitor of Type II 5α-reductase, using in vitro microsome models. Epristeride is considered a potential therapeutic alternative for benign prostatic hyperplasia and its metabolites were analyzed using liquid chromatography–high resolution mass spectrometry. The research identified three primary metabolites: two Phase I oxidation products (M1 and M2) and one Phase II glucuronidation product (M3). Among the five CYP450 isoforms examined, CYP3A4 was found to play a dominant role in epristeride metabolism. The study also identified five key target proteins (ESR1, CYP19A1, STAT3, AKR1C3, and CYP17A1) with which the Phase I metabolites showed significant binding potential, while the Phase II metabolite exhibited lower binding stability. These findings enhance the understanding of epristeride's metabolic pathways and its potential impact on doping control.