Answer to Practice Problem #4 Dose- and Time-Dependent Pharmacokinetics Tutorial:

 

 

 

A low doses, tissue binding is not saturated. However, as dose is increased, the tissue binding becomes saturated and the V_ss will decrease as one increases the dose. This is easily seen by the relationship

V_ss = V_P + (f_up/f_ut)V_T

 

As dose increases and tissue binding becomes saturated, the f_ut increases. If you increase f_ut while holding all other variables constant, the V_ss will decrease. (Note: The curve will look smoother than I have drawn it here, but I am working with the limitations of the drawing program that is compatible with html files.) The lowest the V_ss can decrease is when f_ut becomes so large that (f_up/f_ut)V_T becomes very small and V_ss = V_P.  That is why the curve flattens out at the higher doses.

 

 

 

Last revised 07/14/05

 

ã 2005 -  Craig K. Svensson, Pharm.D., Ph.D.

 

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