Concepts in Clinical Pharmacokinetics

50

Clinical Correlate
This lesson describes a one-compartment,
first-order, IV bolus pharmacokinetic model.
It is used only to illustrate certain math
concepts that will be further explored with
the more commonly used IV intermittent
infusion (i.e., IV piggyback) models described
in Lesson 5. Consequently, read this IV
bolus section only for general conceptual
understanding, knowing that it is seldom FIGURE 4-2.
Plasma drug concentrations resulting from a second dose.
applied clinically.
The dosing interval is the time between admin-
istrations of doses. The dosing interval, symbolized
Intravenous Bolus Dose Model by the Greek letter tau (τ), is commonly determined
by a drug’s half-life. Rapidly eliminated drugs (i.e.,
Although not used often clinically, the simplest
those having a short half-life [T ½]) generally have
example of multiple dosing is the administration of
to be given more frequently (shorter τ) than drugs
rapid IV doses (IV boluses) of drug at constant time
with a longer half-life.
intervals, in which the drug is represented by a one-
compartment model with first-order elimination If a drug follows first-order elimination (i.e., the
(i.e., one-compartment, first-order model). fraction of drug eliminated per unit of time is con-
stant), then plasma drug concentrations after mul-
The first dose produces a plasma drug concen-
tiple dosing can be predicted from concentrations
tration versus time curve like the one in Figure 4-1.
after a single dose. This method uses the principle
C0 is now referred to as Cmax, meaning maximum
of superposition, a simple overlay technique.
concentration, to group it with the other peak con-
centrations that occur with multiple dosing. If the early doses of drug do not affect the phar-
macokinetics (e.g., absorption and clearance) of
If a second bolus dose is administered before the
subsequent doses, then plasma drug concentration
first dose is completely eliminated, the maximum
versus time curves after each dose will look the same;
concentration after the second dose (Cmax 2) will be
they will be superimposable. The only difference is
higher than that after the first dose (Cmax 1) (Figure
that the actual concentrations are higher until steady
4-2). The second part of the curve will be similar
state is achieved because drug has accumulated.
to the first curve but will be higher (have a greater
concentration), because some drug remains from Recall that the y-intercept is called C0, and the
the first dose when the second dose is administered. slope of the line is –K. Furthermore, the drug con-
centration at any time (Ct) after the first IV bolus
dose is given by:

ln Ct = ln C0 – Kt (See Equation 3-2.)

or:

C t = C 0e − Kt

A second IV bolus dose is administered after the

dosing interval (τ) but before the first dose is com-
pletely eliminated. Because Ct = C0e–Kt at any time (t)
after the first dose, it follows that:
FIGURE 4-1.
Plasma drug concentrations after a first dose. C min1 = C max 1 e − Kτ