An Open‐Label, Single‐Dose, Human Mass Balance Study of Amenamevir in Healthy Male Adults

摘要

Abstract Amenamevir is an inhibitor of the helicase‐primase enzyme complex developed for the treatment of varicella zoster virus. This mass balance study investigated the absorption, metabolism, and excretion of a single dose (200?mg) of 14 C‐labeled amenamevir in healthy male volunteers. Blood, urine, and feces samples were collected for up to 8 days after the dose. Safety and tolerability were assessed through voluntary reporting of adverse events, physical examination, and clinical laboratory testing. Amenamevir was rapidly absorbed, with a median time to peak drug concentration of 1.0 to 1.5?hours and a plasma half‐life of 8 to 9?hours. Overall, 95.3% of the administered dose was recovered, with the majority of radiolabeled drug excreted in feces (74.6%) followed by urine (20.6%). The major route of elimination was fecal, with around 70% of the dose excreted as metabolites and 0.1% as the unchanged drug. Metabolic profiling revealed that predominantly radiolabeled amenamevir (80%) and its hydroxyl metabolite R5 (up to 7.1%) were present in plasma. Single‐dose amenamevir was well tolerated; 3 transient and mild adverse events were reported in 3 subjects. Overall, 95% of a single 200‐mg dose of amenamevir was eliminated by 168?hours after the dose, with the major route of elimination being fecal.