Answer the following questions:

(a) What are the objectives of the Bischoff PBPK model? What useful predictions is the model capable of making? How is the model able to translate results from mice to humans?

(b) What are the simplifying assumptions of the model? Why are some organs included in the model while others are excluded? What additional organs would you include for an antidepressant drug? What organs would you include for the drug Lithium (which is used for the treatment of pregnant bipolar women, see paper on by Horton - Tuerk-Cook-Dhur jati)

(c) Verify the mass balance equations for the kidney compartment in the Bischoff model? Explain the physiological meaning of each variable and parameter in the equation.

(d) Run the matlab files provided to you (file sent) and confirm the predictions of the Bischoff model for all organs. Two sets of matlab code are provided, one by a former TA and one that is more structured. Solve the model for the parameters provided for different animals and for the drug, methotrexate (a chemotherapeutic agent). How would you interpret the simulated concentration profiles in terms of physiology? What experiments would you perform to validate the concentration of methotrexate as a function of time for all organs in the model?