TABLE 2
A list of parameters used to build the cellular disposition model for MMAE and T-vc-MMAE
| Parameters | Description | Units | Value (CV%) | Source |
|---|---|---|---|---|
 ,  | Volume of the media compartment for MMAE and T-vc-MMAE model, respectively | ml | 3, 10 | Fixed |
 | Scaling factor to convert the number of molecules to nanomoles. | Unitless |  | Fixed |
 ,  | Volume of each cell | pl | 3.12, 8.14 | Fixed |
 ,  | Doubling time associated with each cell line | H | 40.1, 33.6 | Singh et al. (2016b) |
 | Total concentration of intracellular tubulin | nM | 65 | Shah et al. (2012) |
 ,  | Second-order association and first-order dissociation rates of MMAE binding to tubulin | 1/nM/h, 1/h | 0.0183, 0.545 | Shah et al. (2012) |
 ,  | Second-order association and first-order dissociation rates of T-vc-MMAE binding to HER2 | 1/nM/h, 1/h | 0.37, 0.014 | Maass et al. (2016) |
 | First-order net antibody-HER2-complex internalization rate | 1/h | 0.11 | Maass et al. (2016) |
 | First-order nonspecific deconjugation rate of MMAE from ADC | 1/h | ∼0 | Estimated to be very low value |
 | Average drug/antibody ratio for the formulation of T-vc-MMAE | Unitless | 4.5 | Measured in-house |
 | Number of HER2 receptors on N87 and GFP-MCF7 cells, respectively | Unitless | 950,000, 52,000 | Measured in-house |
 , | First-order rate of protease-induced intracellular ADC degradation and MMAE release | 1/h | 0.353 (9%), 0.03 | Estimated, Maass et al. (2016) |
 | Average first-order influx rate constant for MMAE from extracellular space to intracellular space for N87 and MCF7 cells. | 1/h | 8.33 (8.5%) | Estimated |
 | Average first-order efflux rate constants for MMAE from intracellular space to extracellular space for N87 and MCF7 cells. | 1/h | 0.199 (14%) | Estimated |