BIOPHARMACEUTICS AND

PHARMACOKINETICS
613-T

MISS NIMRA WAHEED

1
 Learning Objectives
• We will study the solved example of two compartment extravascular
model.

• We will draw the graph of the given data and calculate the
pharmacokinetic parameters including rate constants, biological half
life, volume of distribution and area under the curve.

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 Previous Lecture
• In the last lecture we have studied the two compartment
extravascular model.

• We have studied how to draw the graph and calculate the

pharmacokinetic parameters in which we have calculated the
rate constants, biological half life , volume of distribution and
area under the curve.

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SOLVED EXAMPLE OF
TWO COMPARTMENT
EXTRAVASCULAR
EXAMPLE 12-7

The following data were obtained after administration of single 500 mg dose of a drug. Plot
the data and calculate pharmacokinetic parameters associated with this profile. Describe the
pharmacokinetic model that fits these data. Assume F = 1.
SOLUTION

The plasma profile in Fig. 12-13 does not exhibit a smooth curve, indicating that the data
do not appear to fit one-compartment model. The plasma profile exhibits a distributive
phase. Therefore, this profile may reflect a multi-compartnent model and will be feathered
according to a multi-comparunent model, and not according to the method used in one-
compartment model.
 
In order to strip the curve to produce linear segments, the terminal concentration points are to
determine the first-order rate constant and the y-intercept of the first linear segment. The first-
order constant of this straight line is the hybrid rate constant β.
Using natural logarithms, the hybrid rate constant ß is equal to the negative slope of the
straight line represented by the terminal concentration points
FEATHERING

It is noticed that many data points did not fall on this straight line. Those concentration points that
did not fall on this straight line are now feathered with respect to this straight line (straight line
having y-intercept = B, i.e., B-Line of Fig. 12-13). Feathering produces new concentration points
(residual concentrations). The residual concentrations are obtained by subtracting the
concentration at each time point on the straight line having the y-intercept = B from the
corresponding plasma concentration provided in the data.
For example, at 0.2 hour, plasma concentration on the straight line having the y-intercept = B,
is calculated using the modified form of equation (12-3):
The residual concertration at 0.2 hours is obtained by subtracting concentration at 0.2 hours on
the straight line having the y-intercept B from the 0.2 hours plasma concentration provided in
the data:
Residual concentration at 0.2 hours = 27.23 mg/L - 18.84 mg/L = 8.39 mg/L

Similarly, concentration at 0.3 hours on the straight line having the y-intercept = B is calculated
using the modified form of equation (12-3):
SECOND
  FEATHERING

The feathering process is continued using terminal concentration points of residual

concentrationssquares in Fig. 12-14). The first-order rate constant of the terminal two points of
residual concentrations(shown as squares in Fig. 12-14) is and is determined from the slope of the
terminal residualconcentration points (squares in Fig. 12-14). The first-order rate constant ris
calculated as follows:

The second residual concentration at 0.2 hours is obtained by subtracting concentration at 0.2
hours on the straight line having y-intercept = P from the 0.2 hours plasma concentration obtained
during
the previous feathering process (squares in Fig. 12-14).
At 0.2 hour, thbe plasma concentration on the straight line having y-intercept = P is calculated
using equation (12-30):
Therefore, residual concentration at 0.2 hours is 39.33 mg/L - 8.39 mg/L = 30.94 mg/L.
Similarly, the concentration at 0.3 hours on the straight line having the y-intercept = P is
calculated using equation (12-30):

Therefore, residual concentration at 0.3 hours is obtained by subtracting the concentration at 0.3
hours on the straight line having the y-intercept = P from the 0.3 hours plasma concentration
obtained during the previous feathering process, (squares in Fig. 12-14):34.88 mg/L - 14.42
mg/L = 20.46 mg/L
The second set of residual concentrations obtained during the second feathering process is now
plotted on the graph paper. These residual concentrations are shown as triangles in Fig. 12-15.
The residual concentrations plotted as triangles appear to exhibit a fair degree of linearity, and a
straight line which best describes these points can be drawn using eye-ball judgment. It should
be pointed out that in order to draw the straight line representing the y-intercept A, more
emphasis should be placed on the residual concentrations obtained during the earlier segment of
feathering (plasma profile) than those obtained during the terminal segment of feathering.
The residual concentrations are obtained as a result of subtracting a relatively small number from
another small number. Therefore, if the residual concentration point during the second feathering was
actually 0.1 mg/L, but it got rounded off to 0.3 mg/L , the concenration point plotted on the semi-
logarithmic graph paper is more likely to appear non-linear when actually the point may be on the
straight line. Therefore, during the second feathering, residual concentrations obtained for the later
segment of the plasma profile may not necessarily be accurate, but may exhibit approximate values of
the residual concentrations.

The first-order rate constant of the straight line generaled during second feathering is α, and the y-
intercept of this straight line is A. According to equation (12-28), B + P = A, therefore, y-intercept, A
is

A = B + P = 20 mg/L + 50 mg/L = 70 mg/L

The first-order rate constant, α, of this straight line (having the y-intercept = A) is detemined from the
slope of this sıraight line uşing two points which fall on this straight line.
SCHEMATIC REPRESENTATION

DESCRIPTION BY EQUATION
Summary:
• We have studied the solved example of two compartment
extravascular model.

• We have studied how to draw the graph and calculate the

pharmacokinetic parameters
Further Reading and References

• Book: Biopharmaceutics and pharmacokinetics by PL Madan

• Chapter 12

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