THE LABORATORY IN DRUG THERAPY
The objective of drug therapy is to administer
drugs in such a way as to maximize the chances of
achieving the desired therapeutic goals while
minimizing the risk of or severity of unwanted side
effects. This objective is met by the selection of the
appropriate drug or drugs, the prescription of an
appropriate dosing regimen, and the monitoring of
the therapy. Laboratory studies can aid in all of
these tasks. Laboratory methods used to direct the
selection of appropriate drugs for antimicrobial and
anticancer therapy have already been discussed in
earlier chapters. Laboratory studies can also provide
measures of organ function that can be used to
individualize the initial dosing regimen and labora-
tory monitoring of plasma drug concentrations can
be used to evaluate therapy and guide adjustment of
the dosing regimen. The latter two uses of the labo-
ratory are considered here.
DRUG DISPOSITION
The location in the body at which a drug has an
effect, whether therapeutic or toxic, is referred to as
a “site of action” or an “effect site” of the drug.
Occasionally a drug is delivered directly to its site of
action but, in the majority of cases, the drug first
enters the circulation and then distributes to the sites
at which it will have its effects (Figure 12.1). In
this way, the circulation serves as the source of
supply of the drug with the plasma drug concentra-
tion being the driving force for drug entry into the
effect site. Hence, the kinetics of drug disposition in
the plasma determines the time course of the drug
effects. It is not the only determinant—the kinetics
of drug disposition within the effect site and the
kinetics of cellular response to drug are also impor-
tant—but it is the determinant that can most readily
be evaluated and manipulated clinically.
The elements of drug disposition in the plasma
are most clearly demonstrated following bolus intra-
vascular injection of drug. Almost instantaneously,
drug distributes into the various anatomic sites to
which it has rapid access. The initial plasma drug
concentration, C(0), reflects the distribution of drug
throughout the plasma and these rapidly accessible
sites. The initial volume of distribution, V
o
, quanti-
fies the extent of rapid distribution of drug,
C
(
0
) =
dose
V
o
Drug Therapy
12-1
Figure 12.1
A model of the disposition of drugs. The site of action of a drug may be the plasma, a rapidly accessible tissue
site, or a slowly accessible tissue site. In addition, the liver and the kidneys may be sites of action as well as organs of
elimination.
ELIMINATION
plasma and rapidly
accessible sites
DISTRIBUTION
INPUT
slowly accessible
sites
intravascular
oral
portal
circulation
local
catabolism
hepatic
elimination
renal
elimination
liver
Chapter 12
DRUG THERAPY
© 2001 Dennis A. Noe
