title: The relationship between in vivo antiviral activity and pharmacokinetic parameters of peramivir in influenza virus infection model in mice.
abstract: The purpose of this study was to investigate the relationship between pharmacokinetic (PK) parameters of intravenous (IV) peramivir and in vivo antiviral activity pharmacodynamic (PD) outcomes in a mouse model of influenza virus infection. Peramivir was administrated to mice in three dosing schedules; once, twice and four times after infection of A/WS/33 (H1N1). The survival rate at day 14 after virus infection was employed as the antiviral activity outcome for analysis. The relationship between day 14 survival and PK parameters, including area under the concentration-time curve (AUC), maximum concentration (Cmax) and time that drug concentration exceeds IC95 (T(>IC95)), was estimated using a logistic regression model, and model fitness was evaluated by calculation of the Akaike information criterion (AIC) index. The AIC indices of AUC, Cmax and T(>IC95) were about 114, 151 and 124, respectively. The AIC of AUC and T(>IC95) were smaller than that of Cmax. Therefore, both AUC and T(>IC95) were the PK parameters that correlated best with the antiviral activity of peramivir IV against influenza virus infection in mice.
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Izawa
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kitano
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Baba
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noshi
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seki
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Drug Developmental Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Kanazu
authors.affiliation: Drug Developmental Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamimori
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Homma
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan; Research Center for Zoonosis Control, Hokkaido University, Hokkaido, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan; Research Center for Zoonosis Control, Hokkaido University, Hokkaido, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan; Research Center for Zoonosis Control, Hokkaido University, Hokkaido, Japan. Electronic address: akihiko.sato@shionogi.co.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamano
mesh_terms: D000146:Acids, Carbocyclic; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003517:Cyclopentanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir
keywords: Influenza; Neuraminidase inhibitors; PK/PD analysis; Peramivir