a Parameters Fixed | ||||
---|---|---|---|---|
Dose | µg/kg | 1500 | ||
Duration of infusion | Min | 90 | ||
Qliver | ml/min/kg | 20.7 | ||
Vliver | ml/kg | 24.1 | ||
b Parameters to estimate | ||||
ID | min | Max | ||
1-5 | Kp,liver | - | 0.1 | 10 |
6-11 | CLr | ml/min/kg | 1 | 100 |
11-15 | CLbile | ml/min/kg | 1 | 100 |
16 | CLCES,1 | ml/min/kg | 1 | 100 |
17 | CLCES,2 | ml/min/kg | 1 | 100 |
18 | CL3A4,1 | ml/min/kg | 1 | 100 |
19 | CL3A4,2 | ml/min/kg | 1 | 100 |
20 | CLUGT | ml/min/kg | 1 | 100 |
21-25 | kfeces | /min/kg | 0.001 | 0.1 |
26-30 | ka | /min/kg | 0.001 | 0.1 |
31-35 | kLI | /min/kg | 0.001 | 0.1 |
36-40 | ktransit | /min/kg | 0.001 | 0.1 |
41-45 | CL12 | ml/min | 1 | 100 |
46-50 | k21 | min-1 | 0.1 | 10 |
51-55 | Vrapid | ml/kg | 10 | 1000 |
56* | CLbile,T-tube/CLbile,transit | - | 0.1 | 10 |
We used the same initial ranges for these parameters in irinotecan and the metabolites | ||||
* Fixed and set to be zero when analyzing the OC group. | ||||
c Objective values | ||||
ID | OC | BDC | ||
1 | Urinary accumulation µg/kg | irinotecan | 427 | 412 |
2 | SN-38 | 8.20 | 17.0 | |
3 | SN-38G | 57.6 | 227 | |
4 | NPC | 2.67 | 1.70 | |
5 | APC | 42.5 | 146 | |
6 | Fecal accumulation µg/kg | irinotecan | 616 | 118 |
7 | SN-38 + SN-38G | 162 | 52.6 | |
8 | NPC | 25.9 | 6.05 | |
9 | APC | 158 | 31.4 | |
10 | Biliary accumulation µg/kg | irinotecan | - | 349 |
11 | SN-38 | - | 8.32 | |
12 | SN-38G | - | 50.5 | |
13 | NPC | - | 5.68 | |
14 | APC | - | 73.8 |