The relationship between in vivo antiviral activity and pharmacokinetic parameters of peramivir in influenza virus infection model in mice.

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Kodama M, Yoshida R, Hasegawa T, Izawa M, Kitano M, Baba K, Noshi T, Seki T, Okazaki K, Tsuji M, Kanazu T, Kamimori H, Homma T, Kobayashi M, Sakoda Y, Kida H, Sato A, Yamano Y

The relationship between in vivo antiviral activity and pharmacokinetic parameters of peramivir in influenza virus infection model in mice.

Antiviral Res. 2014 Sep;109:110-5. doi: 10.1016/j.antiviral.2014.06.016. Epub 2014 Jul 2.

PubMed ID

24997412 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Peramivir	Neuraminidase	Protein	Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)	Unknown	Not Available	Details