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. Author manuscript; available in PMC: 2021 Jan 15.
Published in final edited form as: AAPS J. 2020 Jan 15;22(2):29. doi: 10.1208/s12248-019-0391-1

Table II:

Model Parameters

Parameter Value Unit Description Reference
CLTT 1.74 × 10−9 L/s Total antibody clearance Estimated (13)
CL2 2.31 × 10−8 L/s Antibody clearance for compartment 2 Estimated (13)
CLDEC 1.74 × 10−9 L/s Deconjugation rate Estimated (12)
V1 1.2 × 10−3 L Volume central compartment Estimated (13)
V2 1.5 × 10−3 L Volume peripheral compartment Estimated (13)
kon 7.1 × 105 M−1s−1 T-DM1 binding rate constant (18)
Kd 0.5 nM T-DM1 dissociation constant (18)
koff 3.5 × 10−4 s−1 T-DM1 dissociation rate constant (18)
ke 3.3 × 10−5 s−1 Internalization rate constant (19)
kdeg 8 × 10−6 s−1 T-DM1 lysosomal degradation rate constant (20)
kloss 3.94 × 10−5 s−1 Cytotoxin loss rate constant Estimated (21)
DAR 3.5 - DM1 to antibody ratio (22)
Rs 2.75 × 10−11 M/s Target synthesis (14)
HER2o* 5 × 104-2 × 106 receptors/cell Total targets per cell Varied
ε 0.24 - Intracellular void fraction (23)
D 1 × 10−11 m2/s Diffusivity (14)
P 3 × 10−9 m /s Vascular permeability (24)
Pmax 0.014 - Maximum probability for cell killing Calibrated
Km 800 nM Michaelis-Menten constant Calibrated
td (in vivo) 5–17 days In vivo doubling time Calibrated
td (in vitro) 1–2.5 days In vitro doubling time Estimated
*

1 million receptors per cell corresponds to 833nM receptors where each cell occupies about 2× 10−12 L.