Fig 1.
Schematic diagram of the oseltamivir PK model.
Fig 2.
Flowchart of method used in model fitting.
Table 1.
OP and OC PK parameters in uninfected ferrets following an oral dose of oseltamivir.a
Fig 3.
Diagnostic plots for the PK model from influenza-inoculated ferret data from studies 1 and 2.
Closed squares and open circles are for animals inoculated with influenza A and influenza B, respectively. Diagnostic plots include (A) predicted versus observed, (B) weighted residuals versus predicted, and (C) weighted residuals versus time since the last dose. The dashed lines are loess curves.
Fig 4.
Diagnostic plots for the PK model from uninfected ferret data from studies 1 to 3.
Diagnostic plots include (A) predicted versus observed, (B) weighted residuals versus predicted, and (C) weighted residuals versus time since the last dose. The dashed lines are loess curves.
Fig 5.
Post-hoc fits in representative ferrets.
Observed and simulated OC PK in representative ferrets from studies 1 and 2: (A) rich PK in an H5N1-inoculated ferret administered a 12.5 mg/kg OP dose; (B) rich PK in an uninfected ferret administered a 5.0 mg/kg OP dose; (C) sparse PK in an H5N1-infected ferret administered 25.0 mg/kg OP q12h; (D) sparse PK in an H3N2-infected ferret administered 12.5 mg/kg OP every twelve h (q12h); (E) PK for an uninfected ferret in the PK control group administered 0.76, 3.8, and 19.0 mg/kg OP on days 1, 3, and 5, respectively; and (F) sparse PK in a ferret inoculated with influenza B/Yamagata/16/1988 influenza virus administered 3.8 mg/kg OP q12h.
Table 2.
Selected PK parameters and clinical signs in ferrets challenged with influenza A viruses (Study 1).
Table 3.
Selected PK parameters and clinical signs in ferret challenged with influenza B virus (Study 2).
Table 4.
OC PK parameters estimated in ferrets with and without anesthesia.
Table 5.
OC PK parameters estimated in uninfected and influenza virus-infected ferrets.
Fig 6.
Monte Carlo simulation of steady-state OC PK at a 5.08 mg/kg OP dose.
The thin solid curves are simulated PK for 100 individual ferrets, the open curves are the 10th–90th percentile, and the thick solid curve is the median OC concentration-time profile.
Table 6.
Monte Carlo simulation parameters and covariance matrix for the OC PK model.
Table 7.
OC PK parameters estimated from Monte Carlo simulations for ferrets inoculated with influenza A or B viruses.