Presiding Officer Training module 2024 lok sabha elections
Pharmacokinetics: Lecture four
1. Extravascular
Administration
Anas Bahnassi PhD RPh
One compartment Model
2. LECTURE’S OBJECTIVES
• Upon completion of this lecture, the student will able to:
• Calculate plasma drug concentration at any given time after the
administration of an extravascular dose of a drug, based on known or
estimated pharmacokinetic parameters
• Interpret the plasma drug concentration versus time curve of a drug
administered extravascularly as the sum of an absorption curve and an
elimination curve
• Employ extrapolation techniques to characterize the absorption phase
• Calculate the absorption rate constant and explain factors that influence
this constant
• Explain possible reasons for the presence of lag time in a drug’s absorption
• Calculate peak plasma drug concentration, (Cp)max, and the time, (tmax)at
which this occurs
• Explain the factors that influence peak plasma concentration and peak time
• Decide when flip-flop kinetics may be a factor in the plasma drug
concentration versus time curve of a drug administered extravascularly.
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Anas Bahnassi PhD 2011
3. Xa Ka
X
We Need the following info:
Xu
1. Equation for determining the plasma concentration at any time t.
2. Determination of the elimination half life (t½) and rate constant (K or
Kel).
3. Determination of the absorption half life (t½)abs and absorption rate
constant (Ka).
4. Lag time (t0), if any.
Anas Bahnassi PhD 2011
5. Determination of the apparent volume of distribution (V or Vd) and
fraction of drug absorbed (F).
6. Determination of the peak time (tmax).
7. Determination of the peak plasma or serum concentration, (Cp)max.
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8. Calculating Absorption Rate
Constant (ka)
Method of Residuals
Feathering Method
Time (h) Observed Plasma Extrapolated Plasma (������������)������������������������ = ������������������������������ − ������������������������������
Concentrations Concentrations
(Cp)observed (Cp)extrapolated
Time values Values only from the Values only from the Differences between
corresponding absorption phase extrapolated portion of extrapolated and observed
to observed (i.e. all values prior to the plot of plasma values for each time in the
plasma reaching maximum concentration–time absorption phase (units,
concentrations or highest plasma (units, e.g. (mgmL1) e.g. mgmL-1)
for absorption concentration) (units,
phase only e.g. mgmL-1)
������������ ������������0
������������������������������������ = ������ −������������ ������
������(������������ − ������)
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Anas Bahnassi PhD 2011
9. Calculating Absorption Rate
Constant (ka)
Method of Residuals
Feathering Method
������������
Slope=−
2.303
Anas Bahnassi PhD 2011 9
10. Lag Time (t0)
Theoretically, intercepts of the terminal linear portion
and the feathered line should be the same; however,
sometimes, these two lines do not have the same
intercepts, Sometimes absorption starts after
administration, this delay may be contributed to:
• Slow tablet disintegration
• Slow and/or poor dissolution
• Incomplete wetting of drug particles
• Poor formula
• Delayed Release formula
Anas Bahnassi PhD 2011 10
11. Negative Lag Time (t0)
The presence of a negative lag time may be attributed to
inadequate data points in the absorption phase as well
as in the elimination phase. Another possible reason
may be that the absorption rate constant is not much
greater than the elimination rate constant.
Anas Bahnassi PhD 2011 11
12. Analysis of Absorption
������������ ≫ ������ Rate Constant
Quicker Faster Onset ������������ for a given drug can
Absorption of Action change as a result of:
• Changing the formulation
• Changing the dosage form
or the extravascular route
of administration.
• Administration of a drug
with or without food.
13. Apparent Volume of
Cannot be calculated from plasma Distribution(Vd)
drug concentration data alone
WHY?
The fraction of drug absorbed (F) is
not known.
If the drug is 100 percent
absorbed; F=1 then
������������ ������������0
������������������������������������������������������ = If F is not known then it is best to
������(������������ − ������)
������
calculate
������
������ ������������ ������0 1
= ( )
������ (������������ −������) ������������������������������������������������������
Anas Bahnassi PhD 2011 13
16. Significance of Peak Time(tmax)
• To determine comparative bioavailability and/or
bioequivalence
• To determine the preferred route of drug administration and
the desired dosage form for the patient
• To assess the onset of action.
Significance of Peak
Concentration(Cmax)
• Used to determine the comparative bioavailability and/or the
bioequivalence between two products.
• Used to determine the superiority between two different
dosage forms or two different routes of administration
• Correlates with the pharmacological effect of a drug.
Anas Bahnassi PhD 2011 16
17. Plot the data and, using the plot, determine
Question
the following.
a. The elimination half life (t1/2) for each dose.
b. The elimination rate constant (K) for each
dose.
c. The absorption half life, (t1/2)abs, for each
dose.
d. The absorption rate constant (Ka) for each
dose.
e. The observed and computed peak time (tmax)
for each dose.
f. The observed and computed peak plasma
concentrations, (Cp)max, for each dose.
g. The y-axis intercept for each dose.
h. The apparent volume of distribution (V).
i. The fraction of drug absorbed (F).
j. The characteristics of a plot on rectilinear
paper of peak time (tmax) against the
administered dose (then make an important
observation).
k. The characteristics of a plot on rectilinear
paper of peak plasma concentrations, (Cp)max,
i. Lag time if any.
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Anas Bahnassi PhD 2011