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. 2016 Mar 15;114(6):669–679. doi: 10.1038/bjc.2016.40

Table 1. Parameter estimates for the integrated semimechanistic PK/PD model for vemurafenib and abemaciclib in mice bearing colo-205 or A375 xenograft tumours.

Parameter Colo-205 xenograft tumours A375 xenograft tumours (model estimation) A375 xenograft tumours (external validation)
Biomarker model
Imax 0.907 (1.7) * *
IC50,Abemaciclib (ng ml−1) 4.99 (21) * *
IC50,Vemurafenib (ng ml−1) 16 800 (7.7) **
kout,pMEK (h−1) 1.76 (31) **
kout,Cyclin D1 (h−1) 0.175 (5.9) **
γCyclin D1 5 (fixed) **
kR (h−1) 0.154 (6.3) * *
kG1S (h−1) 0.631a 0.618a **
kSG2 (h−1) 0.0947a 0.445a **
kMG1 (h−1) 0.272a 1.98a **
kel (h−1) 0.0463 (29) * *
γpRb 0.458 (16) * *
kout,Total Rb (h−1) 0.0524 (38) * *
Tumour model
λ0 (h−1) 0.00290 (9.2) 0.00350 (5.4)
λ1 (mg h−1) 5.16 (41) 6.31 (14)
ω0 (mg) 26.6 (19) 114 (2.9)
kdeath,pERK (h−1) 0.0128 (29) **
kout,modulator (h−1) 0.00191 (64) **
Scalar 0.0000616 (26) **
kdeath,Rb (h−1) 0.00990 (41) **

For all fitted parameters, standard error of the estimate (%) is given within parentheses.

Estimates of interindividual variability and residual error are provided in Supplementary Table 3.

—, Not used in estimation or simulation.

*Simulation performed using parameter estimate obtained from colo-205 xenograft tumour data.

**Simulation performed using parameter estimate obtained from A375 xenograft tumour data.

a

Calculated from literature baseline values of cell density in the respective cell line.