Bringing numbers to life – the use of a laboratory model system to illustrate key parameters and
their interactions in pharmacokinetics
S.J.Tucker and G.M.Hawksworth
School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen
[email protected]
The key variables
Background
• Pharmacokinetics describe the interaction between
drugs and an organism
• It involves derivation of many complex mathematical
and graphical expressions
• The mathematical nature of pharmacokinetics means
the precise meaning of many of the parameters involved
is not always clear to students
• Traditionally student feedback suggests a lack of
understanding of this part of their pharmacology degree
• Appreciation of pharmacokinetics is key to drug
administration and safe use of drugs clinically
A simple model system
• A hydraulic model system that represents a rodent sized
organism has been developed to give key
pharmacokinetic variables physical, measureable form
concentration at time zero ( g/ml)
• Volume of distribution (volume in beaker in Fig 1)
 volume that drug is diluted in
• Clearance (rate of pumps in Fig 1)
 rate of drug removal
Experimental (from graph)
Theoretical
From graph
From slope
Theoretical (CL = Kel
x VD)
Reference Expt
180
200
15
15.1
13.9
Volume Expt
75
100
26.5
26.7
27.7
Clearance Expt
200
200
7
7.0
6.93
Table 1: Experimental values and theoretical values
Use of real data to derive and determine values
reinforces their meaning and inter-relationships to
students.
• Concentration half time
 how long drug persists in system
Experiments performed:
1. Reference experiment:
 Volume = 100 ml; Clearance = 5ml/min
Extrapolation to clinical scenarios
• Follow up questions in report address what these
parameters and changes in them mean in a clinical setting
2. Volume experiment:
 Volume = 200 ml; Clearance = 5ml/min
e.g. What implications might the above results have on
administering drugs to elderly patients who typically have a
lower volume of distribution and lower renal/hepatic function
compared to younger adults?
3. Clearance experiment:
 Volume = 100 ml; Clearance = 10 ml/min
pumps mirror effect of kidneys/liver in removing drug from system
Student feedback
Results – theoretical vs experimental values
precise quantity of drug
added to “beaker”
concentration half time (min)
1000
The model system practical complimented the lecture-based
pharmacokinetics teaching well
The use of the model system helped me understand
pharmacokinetics better
Reference Expt
Figure 1: The hydraulic model system. The volume in the
beaker represents the volume of the model organism to
which a yellow drug is added. The pumps represent
progressive clearance of drug from the system and also
provide a route for sampling the solution for quantification.
The model drug
• A yellow solution – potassium dichromate
• Yellow colour allows visualisation of drug in the
model system and can be quantified using
spectrophotometer
Clearance Expt
100
70
70
60
60
% PA3004 students
samples collected
from this tube
% PA3004 students
beaker represents
volume of organism
(volume of distribution)
Drug concentration (ug/ml)
Volume Expt
50
40
30
20
40
30
20
10
10
10
50
0
0
Strongly
agree
Agree
Don't know
Disagree
Strongly
disagree
Strongly
agree
Agree
Don't know
Disagree
Strongly
disagree
Figure 3: Student feedback from 2011/2012 class
1
0
5
10
15
20
25
30
time (min)
35
40
45
Quotes from students:
50
Figure 3: Graph of experimental data
Illustrates construction of graphs and effects that
variables have on graphical data.
Permits
extrapolation
and
pharmacokinetic parameters
calculation
of
key
Very useful for furthering understanding and illustrating
theoretical versus experimental derivation.
“helpful in visualizing all processes”
“the model was easy to understand and allowed us to
visualise what happens when a drug is administered”
“use of model system was useful to understand how
pharmacokinetics work”
“I think the practical really helped my understanding of
pharmacokinetics further from the lectures”