Description of Models and Data

The prediction of human dose from in vitro data can be achieved using the pharmacokinetic model shown in Equation 16.1, which relies on an estimate of Cmin after the first dose as an input and assumes that exposure exceeding the free potency for the entire dosing interval is required to show efficacy and is attained at steady state [59]  

Tau = dosing interval (12 h for this work as this is the default position for most oral projects). 

MECss = minimum effective concentration (potency corrected for protein 

Of the terms determining those in Equation 16.5 above (f, human Eu, and clearance, MECgg), clearance can be predicted from in vitro data [61,62] and is 

It becomes clear that by making the assumptions above, only the following four parameters are needed to estimate human dose using Equation 16.1 clearance, Ks potency, and the fraction unbound in human plasma (Fu). 

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