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(Disposition Parameters Optimization (Mean Profile (Fit & get disp…

- - - - Optimize if required
  - - - Optimize for all subjects
        
        Cluster Cl, Vd, K (compartment constants) with constraints for better optimization w.r.t. Thalf. Use 1+Yhat^2 [importance to lower values]
        
        If no fit is obtained use manual, hypothetical extrapolation of elimination to force fit to elimination phase
        
        Compare Individual vs Mean. Exercise caution to consider outlier subjects and use discretion to select the disposition parameters
        
        Though elimination is more aligned with terminal concentrations, try "unity" as the weighing function to see how elimination impacts Cmax.
- - - - Use optimizer to optimize all subjects. This will further build confidence on the assumed Peff Value
        
        Use Peff alone and use "Unity" weighing function to target Cmax as Peff has more impact on rate of absorption
- - - - Then, revert back to in-vitro solubility values and optimize gastric pH [if required pH of SI can also be evaluated, but its not required] to see the impact. In real conditions only in-vivo pH changes and not solubility. The low solubility in subject is due to his low pH.
        
        If a pH modifier is present in formulation the optimization of solubility makes sense over tweaking subject pH