One-Compartment Open

Model: Intravenous Bolus

Administration
• Oral drug administration is the most
convenient, but intravenous (IV)
administration is the most desirable for
critical care situations.
• For example: antibiotics during septic
infections or antiarrhythmic drugs
during an MI.
• IV administration is also desirable in
• one-compartment open model is the
simplest way to study drug distribution
and elimination processes.
• The one-compartment open model
assumes that the body can be
described as a single, uniform
compartment and that drugs can enter
and leave the body (ie, open model).
• One compartmental open model plus
IV bolus injection is the simplest
model for pharmacokinetic study.
• It assumes that: instantaneous
administration, instantaneous and
rapid distribution throughout the
body, and immediately elimination.
• In reality, drug distribution is not
truly instantaneous but it is
relatively rapid enough that we
can make this assumption for
most drugs.
• This uniform and instantaneous
distribution is termed a well-
• Drug distribution to the tissues
depends upon many factors,
including:
• - blood flow to those tissues
• - affinity of the tissues to the drug
• - ability of the drug to cross the
vascular membranes (i.e. molecular
weight and lipophilicity) …
• The one-compartment open model
considers the body a constant-volume
system or compartment. Therefore, the
Vd for any given drug is generally a
constant.
• If both the Cp and Vd are known, then
the total amount of drug in the body (at
the time in which the plasma sample
was obtained) may be calculated.
• CALCULATION OF k FROM
URINARY EXCRETION DATA
• The elimination rate constant k
may be calculated from urinary
excretion data. The equation used
is: dDu /dt = keDB
• DB can be substituted for D e :
B
0 –kt
Semilog graph of rate of drug excretion versus time
intercept = keDB0
• The slope of the above curve is equal to –k/2.3 and the y
intercept is equal to keDB0.
• For rapid IV administration, DB0 is equal to the dose D0.
Therefore, if DB0 is known, the renal excretion rate constant
(ke) can be obtained.
• Because both ke and k can be determined by this method,
the nonrenal rate constant (knr) can be found as follows:
• K - ke = knr
• Since the other major route of elimination is metabolism, knr
approximately equal to km
• Though urine is produced at an approximate
rate of 1mL/min and collected in the bladder
but it is voided in wider intervals.
• Thus, the drug urinary excretion rate (dDu/dt)
cannot be determined experimentally for any
given instant.
• In practice, an average urinary excretion rate
Du/t, is plotted against the time corresponding
to the midpoint of the collection interval, t* for
the collection of the urine sample.
• Example1
• A single IV dose of an antibiotic was given to a 50-kg
woman at a dose level of 20 mg/kg. Urine and blood
samples were removed periodically and assayed for parent
drug.
• The data in the table below were obtained, find the
elimination rate constant, k, for this antibiotic?
• Solution
• Set up the following table:

Here t* =
midpoint of
collection
period and
t = time
interval for
collection of
urine sample.
• Construct a graph on a semilog scale of Du/t versus t*.
• The slope of this line should equal –k/2.3. But it is usually
easier to determine the elimination t½ directly from the
curve and then calculate k from: K = 0.693/t1/2
• NB:
• - In this problem, t1/2 = 1.0 hour then k = 0.693 h–1.
• - the slope of the log excretion rate constant is a function of
k and not of ke
• A similar graph of the Cp versus t should yield a curve with
a slope having the same value.
•
• An alternative method for the calculation of
the elimination rate constant k from urinary
excretion data is the sigma-minus method, or
the amount of drug remaining to be excreted
method.
• The sigma-minus method is sometimes
preferred over the previous method because
fluctuations in the rate of elimination are
minimized.
• The amount of unchanged drug in the urine can be
expressed as a function of time through the following
equation:

• Where Du is the cumulative amount of unchanged drug

excreted in the urine.
• The amount of unchanged drug ultimately excreted in the
urine, D∞u, can be determined by making time t equal to ∞.
Thus, the term e–kt becomes negligible and the following
expression is obtained:
• Substitution of D∞u for keD0/k in and rearrangement yields.
•

• The equation above can be written in logarithmic form to

obtain a linear equation:

• This last equation describes the relationship for the amount

of drug remaining to be excreted (D∞u - Du) versus time.
Graphing (D∞u - Du) versus time on semilog paper yields a
linear curve with slope of –K/2.303 and the y intercept is
D∞u
Sigma-minus method, or the amount
of drug remaining to be excreted
method, for the calculation of the
elimination rate constant