Biology Reference
In-Depth Information
Table 6.2
Data Used for the Method of Residuals Example Shown in Figure 6.9
Extrapolated concentration
(mg/L plasma)
Time (h)
Plasma
Residual
1
6.534
0.488
6.046
2
4.318
0.468
3.850
4
1.988
0.431
1.558
8
0.614
0.364
0.250
12
0.345
0.308
0.037
16
0.264
20
0.220
24
0.187
Similar to the one-compartment model, the volume of the central compartment is:
Dose
V
=
.
(54)
c
A
+
B
The rate constants α and β are composites of
k
12
,
k
21
, and
k
10
with the relationships:
α
+ =
+
+
10
,
(55)
k
k
k
12
21
αβ
=
k k
.
(56)
1
0
21
The rate constants
k
12
,
k
21
, and
k
10
are determined from the relationships below
(see
Gibaldi and Perrier, 1982
, for derivations):
A
α
+
+
B
β
,
(57)
k
21
=
A
B
=
-
β
,
(58)
k
10
k
21
= = −
α
β
−
.
(59)
k
k
k
12
21
10
Extravascular Dose
A schematic of a two-compartment model with first-order absorption and elimination is
shown in
Figure 6.10
. Absorption and elimination are assumed to occur via the central
compartment only. The plasma concentration as a function of time can be expressed as:
C
t
=
A
exp
(
− +
α
t
)
Bexp
(
− +
β
t
)
Cexp
(
−
k t
).
(60)
0
1
It is often difficult to distinguish the absorption phase from the distribution phase
of the log
C
t
vs.
t
curve, because
k
01
is similar in magnitude to α. Estimation of rate
constants after an extravascular dose often requires data after an intravenous dose to
distinguish between
k
01
and α (
Gibaldi and Perrier, 1982
).
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