TABLE 2

Pharmacodynamic parameter estimates of S 55746 for caspase activity in RS4;11 xenograft mouse models after once-daily oral administration

Parameters (Unit)DefinitionEstimates (RSE%)
δ (ng⋅ml−1)Free drug concentration threshold in plasma40.4 (0.20)
fuUnbound fraction0.015 fixed
kefi (h−1)First-order transfer rate into the effect compartment1 fixed
kefo (h−1)First-order transfer rate from the effect compartment0.202 (1.20)
Kd (ng⋅ml−1)Dissociation constant from Bcl-22.76 fixed
kin (h−1)Production rate of relative caspase activity57.2
kout (h−1)First-order degradation rate of caspase1.23 (11.6)
I50Value of relative Bcl-2 activity for which caspase production is reduced by 50%0.530 (2.40)
γSigmoidicity coefficient5.88 (3.00)
ε expMultiplicative component of the residual error0.230 (8.00)
  • RSE(%), relative standard error computed as the ratio between the S.E. and the parameter estimate multiplied by 100.