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

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.