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Peer-reviewedCC BYPloS one

Pharmacokinetic diversity of baloxavir marboxil across rare avian species.

  • Yo Shimazu1
  • Ryo Daniel Obara2
  • Mariko Miki1,2
  • Hiromi Osaki2
  • Yuto Yoshimoto3
  • Marina Hayashi3
  • Kosuke Toyoda4
  • Miki Ozaki4
  • Ikumi Hanada4
  • Rei Matsumoto5
  • Kaori Ota6
  • Ayumi Yamaguchi6
18 more authors
  • Kosuke Toda6
  • Junko Ishii7
  • Tsuneo Kizaki7
  • Yuzo Hirano8
  • Yuma Sugimoto8
  • Yukiko Watanabe9
  • Keisuke Saito9
  • Masato Kaku10
  • Izumi Ide11
  • Akihiro Sado12
  • Hidefumi Sakai12
  • Kyohei Nishimura2
  • Mayumi Endo1
  • Takahiro Hiono1,13,14,15
  • Norikazu Isoda1,13,14,15
  • Takao Shishido16
  • Yoshinori Ikenaka13,17,18,19
  • Yoshihiro Sakoda1,13,14,15
19 affiliations
  1. 1Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
  2. 2Laboratory for Drug Discovery and Development, Shionogi and Co., Ltd., Toyonaka, Osaka, Japan.
  3. 3Tokyo Sea Life Park, Edogawa-ku, Tokyo, Japan.
  4. 4Adventure World, Nishimuro-gun, Wakayama, Japan.
  5. 5Hyogo Park of the Oriental White Stork, Toyooka, Hyogo, Japan.
  6. 6Tama Zoological Park, Hino, Tokyo, Japan.
  7. 7Tokyo Zoological Park Society, Taito-ku, Tokyo, Japan.
  8. 8Ueno Zoological Gardens, Taito-ku, Tokyo, Japan.
  9. 9Institute for Raptor Biomedicine Japan, Kushiro, Hokkaido, Japan.
  10. 10Shikoku Aquarium, Utazu-cho, Kagawa, Japan.
  11. 11Toyama Outdoor Nature Museum "Nei no Sato", Toyama, Toyama, Japan.
  12. 12Sapporo Maruyama Zoo, Sapporo, Hokkaido, Japan.
  13. 13One Health Research Center, Hokkaido University, Sapporo, Hokkaido, Japan.
  14. 14International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.
  15. 15Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Hokkaido, Japan.
  16. 16Laboratory for Discovery and Disease Research, Shionogi and Co., Ltd., Toyonaka, Osaka, Japan.
  17. 17Laboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
  18. 18Translational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
  19. 19Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{shimazu2026pharmacokinetic,
  title = {{Pharmacokinetic diversity of baloxavir marboxil across rare avian species.}},
  author = {Yo Shimazu and Ryo Daniel Obara and Mariko Miki and Hiromi Osaki and Yuto Yoshimoto and Marina Hayashi and Kosuke Toyoda and Miki Ozaki and Ikumi Hanada and Rei Matsumoto and Kaori Ota and Ayumi Yamaguchi and Kosuke Toda and Junko Ishii and Tsuneo Kizaki and Yuzo Hirano and Yuma Sugimoto and Yukiko Watanabe and Keisuke Saito and Masato Kaku and Izumi Ide and Akihiro Sado and Hidefumi Sakai and Kyohei Nishimura and Mayumi Endo and Takahiro Hiono and Norikazu Isoda and Takao Shishido and Yoshinori Ikenaka and Yoshihiro Sakoda},
  journal = {PloS one},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0361119},
  url = {https://europepmc.org/article/MED/42912701},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Pharmacokinetic diversity of baloxavir marboxil across rare avian species.
AU  - Yo Shimazu
AU  - Ryo Daniel Obara
AU  - Mariko Miki
AU  - Hiromi Osaki
AU  - Yuto Yoshimoto
AU  - Marina Hayashi
AU  - Kosuke Toyoda
AU  - Miki Ozaki
AU  - Ikumi Hanada
AU  - Rei Matsumoto
AU  - Kaori Ota
AU  - Ayumi Yamaguchi
AU  - Kosuke Toda
AU  - Junko Ishii
AU  - Tsuneo Kizaki
AU  - Yuzo Hirano
AU  - Yuma Sugimoto
AU  - Yukiko Watanabe
AU  - Keisuke Saito
AU  - Masato Kaku
AU  - Izumi Ide
AU  - Akihiro Sado
AU  - Hidefumi Sakai
AU  - Kyohei Nishimura
AU  - Mayumi Endo
AU  - Takahiro Hiono
AU  - Norikazu Isoda
AU  - Takao Shishido
AU  - Yoshinori Ikenaka
AU  - Yoshihiro Sakoda
PY  - 2026
DA  - 2026/10/23
JO  - PloS one
DO  - 10.1371/journal.pone.0361119
UR  - https://europepmc.org/article/MED/42912701
AB  - 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.
SN  - 1932-6203
ER  -