Pharmacokinetics and safety of a novel influenza treatment (baloxavir marboxil) in Korean subjects compared with Japanese subjects

Baloxavir marboxil, a novel influenza therapeutic agent, is a prodrug rapidly metabolized into its active form, baloxavir acid, which inhibits cap‐dependent endonuclease. This study evaluated the pharmacokinetics (PKs) and safety of baloxavir acid in healthy Korean subjects and compared them with published data in Japanese subjects. This open‐label and single‐ascending dose study was conducted in 30 Korean male subjects, with a single oral dose of baloxavir marboxil (20, 40, or 80 mg) administered to eight subjects each; additionally, 80 mg was administered to six subjects (body weight >80 kg). Noncompartmental and population PK analyses were performed, and results were compared with those of Japanese subjects. Appropriateness of the body weight‐based dosing regimen was evaluated by simulation. PK profiles of baloxavir acid revealed multicompartment behavior with a long half‐life (80.8–98.3 h), demonstrating a dose‐proportional increase. Baloxavir acid reached peak plasma concentration from 3.5 to 4.0 h postdosing. Body weight was identified as a significant covariate of apparent oral clearance and apparent volume of distribution, which was similar to that observed in Japanese subjects. Body weight‐adjusted analysis revealed that exposure to baloxavir acid did not significantly differ between Korean and Japanese subjects. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate. Based on a PK study, clinical data including dosing regimen developed in Japan were adequately extrapolated to Korea, supporting the approval of baloxavir marboxil in Korean as a new treatment option for influenza.