After an extravascular administration, the amount of drug that reaches the body can be different from the administrated dose, thus in that case the calculation of VD cannot be done.
The distribution volume of a drug depends on: (1) its respective affinities for plasma proteins and blood circulating cells that retain it in plasma; (2) its ability to leave the vessels; and (3) its affinities for the tissues that can attract it. Consider the following mass balance relationship12:
where VP is the plasma volume and VTand CTare the tissue volume and the tissue concentration, respectively. Knowing thatfu — Cu/C and similarly for tissuesfu,T — Cu/Ct, Cu at steady-state being the same in all parts of the body, eqn  becomes:
Dividing by Cufu yields eqn :
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