Biomedical Engineering Reference
In-Depth Information
100
Dg3
R
Dg2
total
10
Dg3
bile
1
0.1
0
30
60
90
120
150
180
Time (min)
(a)
Dg3
R
100
Dg2
total
10
Dg3
bile
1
0.1
0
30
60
90
120
150
180
Time (min)
(b)
FIGURE 23.10.
Fits of the Dg3 data in reservoir (Dg3
R
) and bile (Dg3
bile
) to the ZPBPK
model (Figure 23.3
b
) for the KHB-perfused (without binding) (
a
) and RBC-Alb-perfused (with
binding) (
b
) livers. The solid triangle symbols are observations on the summed amounts of Dg2
in reservoir and bile (% dose); however, the total amount of Dg2 formed (Dg2
total
) predicted,
was underestimated since Dg2 amounts in liver was not accessible for all time points. (From
ref. 89, with permission.)
as 10, 30, and 60% of the total CL
int
,
met
(Table 23.6). Again, the fit to the ZPBPK
model provided reasonable estimates of CL
efflux
,CL
int
,
met
,CL
int
,
sec
, and
f
L
and was
consistent with the data (Figure 23.10) and the observed clearances (Table 23.6).
Simulations are then made to illustrate the various relevant points pertaining to the
removal of digoxin, a poorly cleared compound. When the blood flow rate is increased
from 10 mL/min to 40 mL/min, it is apparent that the flow would not perturb the
concentration profile and decay processes of digoxin, a poorly extracted compound
(Figure 23.11
a
). Whereas when red cell binding is set as nonexistent (
k
pr
=
k
rp
=
0),
the decay profile of digoxin is hastened, and all clearance values, excretory and
metabolic, are increased (Figure 23.11
b
). When albumin binding is further set as
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