Pharmacokinetic diversity of baloxavir marboxil across rare avian species.

High pathogenicity avian influenza virus (HPAIV) poses a serious threat to captive rare birds. Because effective countermeasures are limited, the use of human antiviral drugs to treat HPAIV infections in captive rare birds has been considered. Although the human antiviral drug, baloxavir marboxil (BXM), is not approved for the treatment of influenza virus infection in birds, previous studies demonstrated the antiviral efficacy of BXM in experimental avian models. Pharmacokinetic studies have also revealed substantial interspecies differences following BXM administration, suggesting the need to establish species-specific dosing regimens. In this study, BXM was administered to 14 avian species to optimize dosing regimens for each species. Oral administration of BXM using different methods revealed that drug-food interactions had a limited impact on systemic drug exposure. Pharmacokinetic analysis of BXM and its active metabolite, baloxavir acid (BXA), demonstrated marked interspecies variability in drug exposure, contributing to the development of optimized dosing regimens for each species. Furthermore, systemic exposure to BXA was strongly associated with drug absorption indicators, suggesting that species-specific differences in absorption efficiency largely determine BXA exposure among avian species. This study provides a pharmacokinetic basis for the rational use of BXM in diverse avian species. It contributes to the development of practical antiviral strategies to protect captive rare birds against HPAIVs.