The apparent volume of distribution will often be proportional to the total
body weight of a patient. In fact many V values found in the literature will be
given as so many liter per kilogram total body weight. The assumption made is
that the body composition is unchanged on a percentage basis, thus distribution
will be identical no matter what the patient weighs. This works within some
limits. For example body composition of the very young and the very old may be
quite different from `normal', that is the average subject in whom the
parameter values may have been originally determined. The young and the old
will be discussed in more detail later. Another group of patients in which body
composition may be greatly altered from `normal' is the obese. These patients
have a higher proportion of adipose tissue and lower percentage of water. Thus
for drugs which are relatively polar, volume of distribution values may be
somewhat lower than the total body weight may suggest. For example the apparent
volume of distribution of antipyrine is 0.62 l/kg in normal weight subjects but
0.46 l/kg in obese patients[7]. Other drugs such
as digoxin and gentamicin are also quite polar and tend to distribute into
water rather than adipose tissue.
Protein binding interactions
The role of protein binding in drug interactions can be quite involved[8]. Although drugs may well displace each other
from common binding sites, the clinical (and pharmacokinetic) importance of
these interactions may require considerable investigation. For these effects to
be important one drug must be extensively protein bound, while the displacer
must have a high affinity for the same binding site. Therapeutically the major
criteria is the free drug concentration. One result of a drug interaction is to
tend to produce an increase in free drug concentration, however, that will
cause an increase in elimination and thus an overall reduction in total drug
concentration, potentially maintaining the free concentrations unchanged.
