Chapter 2: Volume of

Distribution
What is volume of distribution (V)?
 It is not a real volume
o It is the parameter relating the concetration of a drug
in the plasma to the total amount of drug in the body.
 E.g., if a drug as a plasma concentration of
10mg/L when there is 1000mg of drug in
the body, the volume of distribution would
be 100L.
 That is dissolving 1000mg of
drug in an imaginary volume of
100L would give a concentration
of 10mg/L.


total amount of drug∈the body ( A )

V=
plasma drug concentration ( C )
 If volume of distribution is an imaginary volume, what is it
determined by?
o The major determinant is the relative strength of
binding (or partitioning) of the drug to tissue
components as compared to plasma proteins.
 If the drug is very tightly bound by tissues
and not by blood, most of the drug in the
body will be ehld in the tissues and very
little in the plasma, so that the drug will
appear to be dissolved in a large volume
and V will be large.
 If a drug is tightly bound to plasma proteins
and not to tissues, V can be very close to
blood volume as in the case for warfarin.
o The above can be summerised by the following
expression, which shows the main determent of V us
the ratio of the fraction of drug unbound in the plasma
to the fraction unbound in the tissues.
o

fractionunbound ∈ plasma ( fu )
V = plasma volume ( V ) +
fractionunbound ∈tissue ¿ ¿
o Molecular size can also have a major impact on V.
 Therapeutic monocolonal antibodies an
immunoglobulin G are excluded from cells
due to their large molecular size.
 Many of these proteins have a V
similar to the plasma volume in
the body.