Biomedical Engineering Reference
In-Depth Information
TABLE 23.8. Simulation Results in Total Hepatic, Metabolic, and Excretion Clearances of E
2
17G when the Influx, Sulfation, Secretory
Intrinsic Clearances for E
2
17G and Desulfation and Secretory Intrinsic Clearances for E
2
3S17G Are Changed Under Linear Conditions for
Both Single Liver Compartment PBPK and ZPBPK Models
Clearances (mL/min) for PBPK
Clearances (mL/min) for ZPBPK
a
CL
liver
,
met
CL
liver
,
met
Intrinsic Clearance (mL/min)
CL
liver
,
ex
CL
liver
,
met
CL
liver
,
tot
CL
liver
,
ex
CL
liver
,
ex
CL
liver
,
met
CL
liver
,
tot
CL
liver
,
ex
Influx intrinsic clearance of
E
2
17G, CL
influx
273
5.8
4.0
9.8
0.70
7.9
3.3
11.2
0.42
546
6.3
4.5
10.8
0.70
8.6
3.2
11.8
0.37
1092
6.7
4.7
11.4
0.70
9.0
2.9
12.0
0.32
Sulfation intrinsic clearance of
E
2
17G, CL
int
,
sult
1.28
8.0
2.8
10.8
0.35
9.9
1.9
11.8
0.19
2.56
6.3
4.5
10.8
0.70
8.6
3.2
11.8
0.37
5.12
4.5
6.3
10.8
1.40
6.9
4.9
11.8
0.71
Biliary intrinsic clearance of
E
2
17G, CL
int
,
sec
0.78
4.5
6.3
10.8
1.40
6.9
4.9
11.8
0.71
1.55
6.3
4.5
10.8
0.70
8.6
3.2
11.8
0.37
3.10
8.0
2.8
10.8
0.35
9.9
1.9
11.8
0.19
Desulfation intrinsic clearance
of E
2
3S17G, CL
int
,
desult
{
M
}
0.60
5.4
5.4
10.8
0.99
7.8
4.0
11.8
0.51
1.19
6.3
4.5
10.8
0.70
8.6
3.2
11.8
0.37
2.38
7.5
3.3
10.8
0.45
9.5
2.3
11.8
0.24
Biliary intrinsic clearance of
E
2
3S 17G, CL
int
,
sec
{
M
}
0.44 7.5 3.3 10.8 0.45 9.5 2.3 11.8 0.24
0.88 6.3 4.5 10.8 0.70 8.6 3.2 11.8 0.37
1.76 5.4 5.4 10.8 0.99 7.8 4.0 11.8 0.51
a
The ZPBPK model was based on uneven sulfation activities of Sult1e1 of 13, 33, and 54%, respectively, in zones 1, 2, and 3 and even distribution of Oatps and Mrp2
for uptake and excretion and evenly distributed desulfation activity of E
2
3S17G.
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