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Clinical pharmacokinetic dosage calculations are conducted using
the easiest possible equations and methods. This is because there
are usually only a few (sometimes as little as 1–2) drug
serum concentrations on which to base the calculations. Drug serum
concentrations are expensive (typically $25–75
each), and obtaining them can cause minor discomfort and trauma
to the patient. This situation is much different than that found
in pharmacokinetic research studies where there may be 10–15
drug serum concentrations used to calculate pharmacokinetic parameters,
and more complex equations can be used to describe the pharmacokinetics
of the drug. Since the goal of therapeutic drug monitoring in patients
is to individualize the drug dose and serum concentrations in order
to produce the desired pharmacological effect and avoid adverse
effects, it may not be possible, or even necessary, to compute pharmacokinetic parameters
for every patient or clinical situation.
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When medications are administered to humans, the body acts as
if it is a series of compartments1 (Figure 2-1). In many
cases, the drug distributes from the blood into the tissues quickly,
and a pseudoequilibrium of drug movement between blood and tissues
is established rapidly. When this occurs, a one-compartment model
can be used to describe the serum concentrations of a drug.2,3 In
some clinical situations, it is possible to use a one-compartment
model to compute doses for a drug even if drug distribution takes
time to complete.4,5 In this case, drug serum concentrations
are not obtained in a patient until after the distribution phase
is over.
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Intravenous
Bolus Equation
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When a drug is given as an intravenous bolus and the drug distributes
from the blood into the tissues quickly, the serum concentrations
often decline in a straight line when plotted on semilogarithmic
axes (Figure 2-2). In this case, a one-compartment model ...