Pharmacokinetics, Disposition, and Biotransformation of Laroprovstat in Humans: In Vivo and In Vitro Evaluations

C]laroprovstat solution was administered for disposition and biotransformation characterization. Based on in vitro studies, CYP3A are the predominant enzymes involved in the oxidative metabolism of laroprovstat, accounting for approximately 90% of laroprovstat metabolism. From the clinical study, laroprovstat is highly orally bioavailable, 78.4%. Laroprovstat was extensively metabolized with most of the dose excreted as oxidative metabolites with some additional conjugation. Only 15% and 6% of the dose was eliminated as parent in the urine and feces, respectively. No major circulating metabolites were identified that require further safety assessment or in vitro evaluation of DDI potential, aligned with the analysis of metabolites in plasma after repeated administration of laroprovstat from the MAD study. Renal elimination of total radioactivity was 64%, compared to 26% in the feces. Laroprovstat does not undergo significant chiral interconversion. Laroprovstat was well tolerated with no new safety concerns. These studies successfully characterized the ADME properties of laroprovstat.