Figure 6

Simulated values of the effects of the cimicoxib for different oral doses of cimicoxib for the 4 endpoints modeled using a PK/PD model in the 8 extensive metabolizer dogs. Effects of cimicoxib vs. time (h) were simulated using the corresponding PK/PD model for different oral doses of cimicoxib (from 0.1 to 8 mg/kg) on the rectal temperature (°C), the normalized vertical ground reaction force of the paw, the creeping speed (m/s) and the overall clinical lameness score. PK and PD parameters used for simulations were the means of those obtained in the 8 extensive metabolizer dogs. The thick line was obtained with 2 mg/kg, the dose that has been selected for confirmatory clinical trials. Beyond this 2 mg/kg dose, the effects were not or marginally increased: the only consequence of the increase in the dose being to increase the duration of the effect.