TABLE 2

Pharmacodynamic parameter estimates of PF02341066 for cMet phosphorylation in athymic mice bearing GTL16 tumors after repeated oral administration of PF02341066 Precision of the estimates is expressed as S.E. in parentheses.


Parameters

Link Model

IDR Model

Combined Model
EC50 (ng/ml) 18.5 (2.65) 4.59 (0.84) 18.5 (2.72)
E 0 1 fixed 1 fixed 1 fixed
E max 1 fixed 1 fixed 1 fixed
ke0 (h–1) 0.135 (0.020) N.A. 0.136 (0.020)
kout (h–1) N.A. 0.159 (0.046) 20.0 (0.8)
OFV
–322
–265
–322
  • IDR model, indirect response model; combined model, indirect response model with effect compartment; EC50, the concentration causing one-half maximum effect; E0, the baseline of cMet phosphorylation; Emax, maximum effect; ke0, the rate constant for equilibration with the effect site; kout, the degradation rate constant; OFV, the objective function value; N.A., not applicable