Biomedical Engineering Reference
In-Depth Information
Apical side (facing intestinal lumen)
(a)
(b)
(c)
(d)
(e)
FIGURE 16.1.
Drug transport routes across the intestinal epithelial cell monolayer: (
a
) pas-
sive transcellular diffusion; (
b
) paracellular diffusion; (
c
) transporter-mediated absorption; (
d
)
transporter-mediated secretion; (
e
) transcytosis.
basolateral membrane of enterocytes, while paracellular permeation occurs through
the gaps between adjacent epithelial cells. The rate-limiting step in paracellular trans-
port is the barrier known as the
tight junctions
, which consists of large complexes
of multiple different proteins that link adjacent cells together to form the intesti-
nal mucosal membrane. Transcellular transport can be further divided into passive
transcellular diffusion, carrier-mediated transport, and transcytosis.
16.2.1. Transcellular Diffusion
Transcellular passive diffusion is the route that many drugs take to permeate the
intestinal epithelium. This type of transport does not require adenosine triphosphate
(ATP) hydrolysis since its driving force is the concentration gradient of the drug,
which makes the drug move toward regions with low drug concentration (e.g., from
the intestinal lumen to the blood). Passive diffusion can be mathematically described
by
Fick's first law of diffusion
:
dM
dtS
=
J
=
P
(
C
1
−
C
2
)
(1)
where
J
is the amount of drug flowing through a unit cross section of a barrier
in unit time, known as flux, and
P
is the permeability coefficient (also called the
permeability).
C
1
and
C
2
are the drug concentrations at the apical and basolateral side
of enterocytes, respectively. It is noteworthy that drug transport within the enterocytes
is ignored when using this equation. In fact, once the drug molecule transports across
the enterocytes, it will rapidly be carried away from the basolateral side by the blood
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