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administration: monitoring
drug in urine
Methods to compute
PK parameters from urinary data
1. the ‘‘amount remaining to be excreted’’
method (ARE); also known as the sigma-
minus method
X u
X Xu
u
Ka K
Ka e Kt K e Kat
Sigma-Minus Method
Generally, when Ka>>K, at certain time point the
absorption process ends (become negligible) as we
referred earlier by the terminal phase. Previous Eqn.
become:
X u Xu
X u
Ka K
Ka e Kt
0-2 50 1.272
2-4 25 2.972
4-8 100 0.915
8-16 200 0.280
16-24 150 0.075
24-32 200 0.011
Sigma-Minus Method:
1- Calculate cumulative amount of drug
eliminated
Cumulative
Time Volume Concentration Amount
Amount
interval (hr) (ml) (mg/ml) (mg)
(mg)
0-2 50 1.272 63.60 63.6
2-4 25 2.972 74.30 137.9
4-8 100 0.915 91.50 229.4
8-16 200 0.280 56.00 285.4
16-24 150 0.075 11.25 296.7
24-32 200 0.011 2.20 298.9
Sigma-Minus Method:
2- Calculate amount remaining to be excreted
(ARE)
ARE
Xu Xu
Cumulative
Time Amount
Amount
interval (hr) (mg)
(mg) (mg)
0-2 63.60 63.6 235.3
2-4 74.30 137.9 161.0
4-8 91.50 229.4 69.5
8-16 56.00 285.4 13.5
16-24 11.25 296.7 2.2
24-32 2.20 298.9 0
Sigma-Minus Method:
3- Plot time (end of interval) vs. log(ARE)
ARE
Xu
2.5
Time
Xu
(hr) Terminal phase
(mg) 2
(straight line)
2 235.3
log(ARE)
1.5
4 161.0
8 69.5 1
16 13.5 0.5
24 2.2
0
32 0 0 5 10 15 20 25 30
time (endpoint of the interval, hr)
Sigma-Minus Method:
4- draw the best fit line to the linear portion of the
curve (terminal phase)
2.5
y = -0.0937x + 2.6045
log(ARE)
1.5
R2 = 0.9991
0.5
0
0 5 10 15 20 25 30
time (endpoint of the interval, hr)
Sigma-Minus Method: Example
The plot of log(ARE) vs. end of the time
interval point of urine collection time gives a
line with a slope equal to –K/2.303
K slope 2.303
1
K 0.0937 2.303 0.22 hr
The rate of excretion method
Xu
Kr X
t
substituting the value of X from previous lecture (oral
equation), we get:
t
Xu K r KaFXo Kt Kat
( Ka K )
e e
Generally, when Ka>>K, at certain time point the
absorption process ends (become negligible) as we
referred earlier by the terminal phase. Previous Eqn.
become:
Xu K r KaFXo Kt
t
( Ka K )
e
The rate of excretion method
Taking the logarithm, we get:
Xu K r KaFXo Kt
log log
t ( Ka K ) 2.303
Thus the plot of dXu/dt vs. mid point of urine
collection time gives a line with a slope equal
to –K/2.303
0-2 50 1.272
2-4 25 2.972
4-8 100 0.915
8-16 200 0.280
16-24 150 0.075
24-32 200 0.011
The rate method:
1- Calculate amount of drug eliminated
Xu
Time Volume Concentration Amount Δt
interval (hr) (ml) (mg/ml) (mg) t
(hr)
mg/hr
0-2 50 1.272 63.60 2 31.80
2-4 25 2.972 74.30 2 37.15
4-8 100 0.915 91.50 4 22.88
8-16 200 0.280 56.00 8 7.00
16-24 150 0.075 11.25 8 1.41
24-32 200 0.011 2.20 8 0.28
The rate method:
4- Plot time (mid of interval) vs. log(dXu/dt)
2
Xu
Time Terminal phase
t 1.5
(h) (straight line)
mg/hr
1
31.80
log (dXu/dt)
1
3 37.15 0.5
6 22.88
0
0 5 10 15 20 25 30
12 7.00
-0.5
20 1.41
28 0.28 -1
time (midpoint of the interval, hr)
The rate method:
5- draw the best fit line to the linear portion of
the curve (terminal phase)
2
1.5
y = -0.0874x + 1.8946
R2 = 1
1
log (dXu/dt)
0.5
0
0 5 10 15 20 25 30
-0.5
-1
time (midpoint of the interval, hr)
The rate of excretion method:
Example
The plot of dXu/dt vs. mid point of urine
collection time gives a line with a slope equal
to –K/2.303
K slope 2.303
1
K 0.0874 2.303 0.2 hr