Table II:
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.