
68 Computational Pharmacokinetics
Unbound Unbound
Bound Bound
Central space Peripheral space
6
?
6
?
FIGURE 4.1: The distribution of drug is at equilibrium determined by protein
binding, assuming only unbound drug passes through barriers
It follows that K
p
= f
u,c
/f
u,p
, which gives us the equation
V
ss
= V
c
+
f
u,c
f
u,p
V
p
.
This shows that it is the fraction of unbound drug that defines the volume
we measure. A drug which is more strongly bound outside the central space
than in the central space will have a larger apparent volume than one that
is more weakly bound. Note that the amount of drug outside the central
compartment over the amount in it is given by
V
p
C
p
V
c