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Table 1 Initial, final, and fixed parameters for CNM

From: Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models

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
  1. a fixed parameters for calculation, b initial parameters to estimate, and c objective values are shown. Minimum and maximum values of the initial ranges were represented for the parameters to estimate. We used the same initial ranges for each of the five parameters for irinotecan and the metabolites, except for #16-20 and #56. We used the same parameter value of #56 for irinotecan and the metabolites. Parameter #56 was fixed and set to be zero and fixed when analyzing the OC group. The total amount of urinary, fecal, and biliary accumulation was normalized to the amount of dose (1500 µg/kg). BDC, bile-duct cancer patients; CL12, clearance from a rapid to a late equilibrium compartments; CLCES,1, metabolic clearance of irinotecan by CES2 to form SN-38; CLCES,2, metabolic clearance of NPC by CES2 to form SN-38; CLbile,total, sum of biliary clearance to a transit compartment and biliary clearance to biliary T-tube; CL3A4,1, metabolic clearance of irinotecan by CYP3A4 to form APC; CL3A4,2, metabolic clearance of irinotecan by CYP3A4 to form NPC; CLR, renal clearance; CLUGT, metabolic clearance of SN-38 by UGT to form SN-38G; k21, kinetic constant from a late to a rapid equilibrium compartment; ka, absorption rate constant; kfeces, kinetic constant for the transit from large intestine to feces; kLI, kinetic constants for the transit from small intestine to large intestine; KP,H, concentration ratio between liver and rapid equilibrium compartment; ktransit, kinetic constant for the transit in bile compartments to small intestine; OC, other cancer patients; QH, blood flow rate in liver; VH, volume of a liver; Vrapid, apparent volume of a rapid equilibrium compartment.