ADME lecture 4 Contents '''

1
ADME lecture 4Contents ...

• Concentration at any time after i.v. injection
• Graphical analysis of data following single
  i.v. bolus

2
Part 1
Concentration at any time after iv injection
3
Predicting concentration at a given time point
C0
4 3 2 1 0
Ct C0.e-Kt
Conc (mg/L)
Ct
t
0 2 4 6 8
10
Time (h)
4
Predicting concentration at a given time point
D 10 mg V 50 L K 0.05
h-1 What conc. after 12 hours? C0 D/V
10mg/50L 0.2mg/L 200µg/L Ct C0 .e-Kt
200µg/L . e-0.05h-1 x 12h 200µg/L .
e-0.6 200µg/L . 0.55 110 µg/L
5
Part 2
Graphical analysis of data following single iv
bolus
6
Linearisation
C0
C0
8 6 4 2 0
2.0 1.0 0.0
Grad -K
Ct C0.e-Kt
LnCt LnC0 - Kt
Conc (mg/L)
Ln Conc (mg/L)
Ct
Ct
0 2 4 6
0 2 4 6 8
10
Time (h)
Time (h)
7
Semi-log plots
1000 100 10 1
3 2 1 0
T (h)
Conc (µM)
Log conc
0 1 2 3
1000 100 10 1
3 2 1 0
Conc
Log conc
0 1 2 3
0 1 2 3
Time (h)
Time (h)
8
Example calculation
500 mg of drug given i.v. at time zero ...
Time (h) Conc (mg/L)
1 17.0
2 14.0
Calculate V, K Cl
4 10.0
6 7.4
8 5.3
10 3.8
12 2.8
9
100 50 30 10 5 3 1
Theoretical C0 19.5 mg/L
Conc (mg/L)
t½ 4.4 h
0 2 4 6 8 10 12
Time (h)
10
Analysis of data following i.v. bolus into a one
compartment sytstem
V D / C0 500mg / 19.5mg/L 25.6
Litres K 0.693 / t½ 0.693 / 4.4h
0.158 h-1 Cl K.V 0.158 h-1 x 25.6 L
4.04 L/h
11
Terms with which you should be familiar ...
Semi-log graph Theoretical C0
12
What you should be able to do

• Correctly number and label the axes of a
  semi-log graph
• Plot Conc versus Time data onto the above graph
• Obtain a theoretical C0 by back extrapolation
• Obtain V from D C0
• Determine half-life from the graph
• Obtain K from half-life
• Obtain Clearance from K V