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

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.