Biomedical Engineering Reference
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100
PP hepatocytes
80
60
40
20
0
0
1
2
3
4
5
(a)
100
PV hepatocytes
80
60
40
20
0
0
1
2
3
4
5
Concentration (
μ
mol/L)
(b)
FIGURE 23.9.
Rates of digoxin uptake by PP and PV isolated rat hepatocytes (
n
=
4): the
fitted lines are the sum of saturable (small dashed lines) and nonsaturable (medium dashed
lines) components. (From ref. 89, with permission.)
TABLE 23.5. In Vitro Metabolism and Transport Data on Digoxin in the Rat Hepatic
Microsomes and Isolated Zonal Hepatocytes
K
m
V
max
PS
uptake
CL
int
(nM)
(pmol/min/mg)
(
L/min/mg)
(
L/min/mg)
Metabolism
d
125,000
362
—
2.90
Transport
Periportal hepatocytes
180
±
112
13
±
8
9.2
±
1.3
83
±
29
Perivenous hepatocytes
390
±
406
18
±
4.9
10.7
±
2.5
111
±
80
Source
: ref. 89; with permission.
a
Saturable component.
b
Nonsaturable or linear uptake clearance.
c
Total hepatocyte uptake clearance is equal to
V
max
/
K
m
+
PS
uptake
under linear conditions; PS
uptake
is the
permeability-surface area product by passive diffusion.
d
Metabolic data from Salphati and Benet.
96
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