Compound |
f
B
|
Kp
GI
|
Kp
Liver
|
Kp
Adipose
|
Kp
NET
| CLU,R[mL/min/kg] | CLU,B[mL/min/kg] |
---|
Irinotecan | 0.37 | 1.00 | 1.00 | 10.0 | 3.00 | 6.15 | 10.6 |
APC | 0.37 | 1.00 | 1.00 | 1.50 | 0.06 | 1.47 | 5.45 |
NPC | 0.37 | 1.00 | 1.00 | 6.00 | 2.00 | 1.49 | 14.5 |
SN-38 | 0.05 | 1.00 | 1.00 | 2.00 | 0.70 | 9.91 | 103 |
SN-38G | 1.00 | 1.00 | 1.00 | 2.80 | 0.08 | 1.44 | 2.03 |
KCZ | 0.01 | 1.00 | 1.00 | 15.0 | 1.50 | 130 | - |
- Blood unbound fraction (f
B
) values for irinotecan and SN-38 were obtained from the published paper by Oliver et al. [45]. The f
B
values for NPC and APC were assumed to be the same as that of Irinotecan. f
B
value for SN-38G was assumed to be 1.00. Urinary and biliary clearances (CLU,R, CLU,B) were defined for unbound blood concentration. CLU,Rand CLU,Bvalues for irinotecan, APC, SN-38, SN-38G were calculated using data from the publish paper [18]. Kp values were determined so that the simulation concentration/time profile fits to the experimental data from Slatter et al. [18].