Biomedical Engineering Reference
In-Depth Information
Apical
Apical
8
PS
p
gp
PS,
a,inf
PS,
a,eff
PS,
a,inf
PS,
a,eff
r = 0.892
P < 0.01
6
PS
b,eff
PS
b,eff
PS
b,inf
PS
b,inf
9
10
Basal
Basal
4
parental cells
MDR1-transfected cells
5
8
3
Blood
Blood
6
7
PS
p
gp
PS
l,eff
PS
l,inf
2
PS
l,eff
PS
l,inf
4
Brain
Brain
2
1
PS
al,inf
PS
al,inf
0
PS
al,eff
PS
al,eff
0
10
20
30
mdr1a
/
1b (
−/−
)mice
k
p, brain
ratio
mdr1a/1b (
+/+
)mice
(a)
(b)
Apical
Apical
PS
a,inf
r = 0.855
P < 0.01
4
PS
p
gp
PS
a,eff
PS,
a,inf
PS
a,eff
12
3
11
PS
b,eff
PS
b,eff
PS
b,inf
PS
b,inf
Basal
Basal
2
7
9
parental cells
MDR1-transfected cells
6
PS
p
gp
PS
m,inf
PS
m,eff
3
4
PS
m,inf
PS
m,eff
10
Mucosa
l
Mucosa
l
5
1
8
2
1
0
0
2
4
6
8
10
12
Serosa
l
Serosal
PS
s,inf
PS
s,eff
PS
s,inf
PS
s,eff
in situ PS product ratio
mdr1a/1b (
−/−
)mice
normal mice
(c)
(d)
FIGURE 19.7.
Prediction of the in vivo Pgp function in the intestine and in brain from in
vitro transcellular transport studies in MDR1-expressing LLC-PK1 cells. (
a
) Schematic dia-
gram illustrating the relationship between the transcellular transport clearance of compounds
in MDR1-expressing and parent LLC-PK1 cells (upper figure) and the brain-to-plasma concen-
tration ratio in mdr1a/1b(
−
/
−
) mice and normal mice (lower figure). The details are discussed
in the text. (
b
) Correlation of the
K
p
,brain
ratio calculated from the in vivo brain-to-plasma
concentration ratio in mdr1a/1b(
−
/
−
) mice and normal mice and the in vitro corrected flux
ratio calculated from the transcellular transport clearance across the LLC-PK1 cell mono-
layer. Each symbol corresponds to an individual substrate. (
c
) Schematic diagram illustrat-
ing the relationship between the transcellular transport clearance of compounds in MDR1-
expressing and parent LLC-PK1 cells (upper figure) and the intestinal absorption clearance
in mdr1a/1b(
−
/
−
) mice and normal mice (lower figure). The details are discussed in the text.
(
d
) Correlation of the PS product ratio calculated from the results of in situ intestinal perfu-
sion studies and the in vitro PS
a-to-b
ratio calculated from the transcellular transport clearance
across the LLC-PK1 cell monolayer. Each symbol corresponds to an individual substrate. [(
a,
b
) From ref. 54; (
c, d
) from ref. 69. With the kind permission of Springer Science and Business
Media.]
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