Table 1.

Summary of model parameters for plasma PK and tumor deposition models

NameValueUnitsDescriptionReference
Plasma PK model parameters
For free irinotecan
ClCPT-111.222e−4L/minPlasma clearance rate of CPT-11Estimated
ClSN-382.138e−5L/minPlasma clearance rate of SN-38Estimated
k12,CPT-118.444e−51/minRate of CPT-11 transport from plasma to peripheral compartmentEstimated
k21,CPT-114.213e−21/minRate of CPT-11 transport from peripheral to plasma compartmentEstimated
k12,SN-382.656e−51/minRate of CPT-11 transport from plasma to peripheral compartmentEstimated
k21,SN-383.44e−41/minRate of CPT-11 transport from peripheral to plasma compartmentEstimated
Vmax,CES,p2.263e−1nmol/minMaximum rate coefficient for CES enzyme in plasma compartmentEstimated
Km,CES,p2.67e5nmol/LMichaelis-Menten constant for CES enzyme in plasma compartmentEstimated
Vp9.46e−5LVolume of plasma compartmentEstimated
Vph0.02LVolume of peripheral compartmentFixed (14)
For nal-IRI
Clnal-IRI1.87e−7L/minPlasma clearance rate of nal-IRIEstimated
ClCPT-111.634e−5L/minPlasma clearance rate of CPT-11Estimated
ClSN-382.957e−6L/minPlasma clearance rate of SN-38Estimated
k12,CPT-111.619e−41/minRate of CPT-11 transport from plasma to peripheral compartmentEstimated
k21,CPT-115.349e−71/minRate of CPT-11 transport from peripheral to plasma compartmentEstimated
Vmax,Release,p8.443e−6nmol/minMaximum rate coefficient for CPT-11 release from nal-IRI in plasma compartmentEstimated
Km,Release,p2.04nmol/LMichaelis-Menten constant for CPT-11 release from nal-IRI in plasma compartmentEstimated
Vmax,CES,p5.943e−2nmol/minMaximum rate coefficient for CES enzyme in plasma compartmentEstimated
Km,CES,p1.198e−5nmol/LMichaelis-Menten constant for CES enzyme in plasma compartmentEstimated
Vp1.12e−3LVolume of plasma compartmentEstimated
Vph0.02LVolume of peripheral compartmentFixed (14)
Tumor deposition model parameters
Qtumor2.119e−6L/minBlood flow rate to tumor(14)
PSnal-IRI7.858e−5L/min/kgTissue permeability coefficient of nal-IRIEstimated
PSCPT-111.851e−3L/min/kgTissue permeability coefficient of CPT-11Estimated
PSSN-382.687e−2L/min/kgTissue permeability coefficient of SN-38Estimated
σnal-IRI3.181e−3Tissue-capillary partition coefficient of nal-IRIEstimated
σCPT-115.24e−1Tissue-capillary partition coefficient of CPT-11Estimated
σSN-382.109e−1Tissue-capillary partition coefficient of SN-38Estimated
kRelease,t1.681e−41/minRate coefficient for CPT-11 release from nal-IRI in tumor tissue compartmentEstimated
Vmax,CES,t2.17e−2nmol/minMaximum rate coefficient for CES enzyme in tumor tissue compartmentEstimated
Km,CES,t2.3e−6nmol/LMichaelis-Menten constant for CES enzyme in tumor tissue compartmentEstimated
Vcap7e−7LVolume of tumor capillary compartment(14)
Vt1e−5LVolume of tumor tissue compartmentFixed