Data Used for Model Parameterization and Validation

Fit parameters are based on data for all three routes these parameter values are then used for the final simulations of these data as well as the simulations for the validation data from these and additional studies. Some of the data used are from Benschop et al, which is a more inclusive technical report of the same study published by van der Schans et however, it is a limited distribution document so data reported solely in this report are not presented here. 

The model is parameterized using the pharmacokinetic data of Benschop et al. and van der Schans et a/. and is validated with the pharmacokinetic data of Trap. All of the animals in the Benschop et al. and van der Sehans et al. ° study received atropine and were artificially ventilated during dosing. The Trap report is not in English, so it could not be determined whether animals received atropine or artificial ventilation during dosing. Since this study and the Benschop et al. and van der Schans et studies appear to have been conducted at TNO in The Netherlands, it is assumed that this study was conducted using a similar protocol. 

Pharmacodynamic data of Lumley et al. are used to parameterize the model, which is then validated with pharmaeodynamic data from Shih et Only 

The model is parameterized using pharmaeokinetie and pharmaeodynamie data from Lumley et al and is validated with pharmaeokinetie and pharmacodynamic data from Benschop et and van der Sehans et The animals in the Lumley et al. study reeeived neither atropine nor artifieial ventilation during exposure, but the Bensehop et aL and van der Sehans et aD° animals received both. The area of exposure to use for simulating the validation dataset is estimated using body weight, dose and dilution rate for the validation dataset and the spread observed for the 60 pg VX kg BW dose. 

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