Table II.
Pharmacodynamic parameter estimates for single and combined effects of DEX and TOF
| Parameter (unit) | Definition | Estimates (CV%) |
|---|---|---|
| Disease-specific | ||
| tonset (h) | Time of disease onset | 339.7 (0.7) |
| kg (/h) | Natural growth rate constant | 0.00103 (75.7) |
| kout (/h) | Loss of edema rate constant | 0.0106 (14.4) |
| kdeg (/h) | Loss of production rate constant | 0.000565 (19.3) |
| Pawss (mm2) | Paw size at steady-state | 98.6 (24.5) |
| Paw0,hC (mm2) | Paw size on day 0 for healthy controls | 68.42 (1.2) |
| Paw0,vC (mm2) | Paw size on day 0 for vehicle control group | 71.10 (1.5) |
| kin0,vC (mm2/h) | Disease production rate constant at tonset for vehicle control group | 1.68 (9.1) |
| Paw0,lT (mm2) | Paw size on day 0 for 1.5 mg/kg TOF group | 68.60 (1.5) |
| kin0,lT (mm2/h) | Disease production rate constant at tonset for 1.5 mg/kg TOF group | 1.69 (9.0) |
| Paw0,hT (mm2) | Paw size on day 0 for 5.0 mg/kg TOF group | 67.78 (1.5) |
| kin0,hT (mm2/h) | Disease production rate constant at tonset for 5.0 mg/kg TOF group | 1.69 (9.0) |
| Paw0,D (mm2) | Paw size on day 0 for 0.225 mg/kg DEX group | 68.23 (1.7) |
| Kin0,d (mm2/h) | Disease production constant at tonset for 0.225 mg/kg DEX group | 1.73 (9.2) |
| Paw0,Com (mm2) | Paw size on day 0 for joint 1.5 mg/kg TOF & 0.225 mg/kg DEX group | 69.50 (1.4) |
| Kin0,Com (mm2/h) | Disease production rate constant at tonset for joint 1.5 mg/kg TOF & 0.225 mg/kg DEX group | 1.66 (9.4) |
| Drug-specific | ||
| Imax,T | Maximum inhibition of TOF on production of paw edema | 0.61 (41.3) |
| IC50,t (ng/mL) | Unbound tissue concentration of TOF at 50% Imax,T | 1.14 (282.5) |
| Imax,D | Maximum inhibition of DEX on production of paw edema | 1 (fixed) |
| IC50,D (ng/mL) | Unbound tissue concentration of DEX at 50% Imax,D | 0.092 (81.4) |
| Drug interaction parameter | ||
| ψ | Interaction term for inhibition of paw edema production | 0.76 (86.2) |