TABLE 5.
Pharmacodynamic parameter estimates for single and combined effects of DEX and NPX on paw edema in CIA rats
| Parameters (Units) | Definition | Estimates (CV%) |
|
|---|---|---|---|
| Females | Males | ||
| Disease-specific parameters | |||
| tonset (h) | Time of disease onset | 258 (0.44) | 307 (0.60) |
| kout (1/h) | Loss of edema rate constant | 0.015 (6.07) | 0.012 (5.37) |
| kdeg (1/h) | Loss of production rate constant | 0.001 (5.98) | 0.001 (8.18) |
| kg (1/h) | Natural growth rate constant | 0.002 (36.0) | 0.002 (29.5) |
| Pawss (mm2) | Paw size at steady-state | 72.16 (6.64) | 103.1 (6.60) |
| Paw0,ng (mm2) | Paw size on day 0 for natural growth group | 52.7 (2.14) | 77.9 (1.53) |
| kin0,c (mm2/h) | Disease production rate constant at tonset for control group | 2.18 (3.94) | 1.72 (4.26) |
| Paw0,c (mm2) | Paw size on day 0 for control group | 58.8 (1.43) | 73.4 (1.58) |
| kin0,D (mm2/h) | Disease production rate constant at tonset for DEX treatment group | 1.93 (4.11) | 1.82 (4.27) |
| Paw0,D (mm2) | Paw size on day 0 for DEX treatment group | 58.9 (1.26) | 73.6 (1.42) |
| kin0,N (mm2/h) | Disease production rate constant at tonset for NPX treatment group | 2.06 (4.19) | 1.79 (4.39) |
| Paw0,N (mm2) | Paw size on day 0 for NPX treatment group | 60.0 (1.29) | 70.2 (1.55) |
| kin0,B (mm2/h) | Disease production rate constant at tonset for combined treatment group | 2.00 (4.33) | 1.80 (4.50) |
| Paw0,B (mm2) | Paw size on day 0 for combined treatment group | 57.7 (1.28) | 74.8 (1.52) |
| Drug-specific parameters | |||
| Iʹmax,N | Maximum inhibition of NPX on production of paw edema | 0.75 (Fixed) | 1 (Fixed) |
| ICʹ50,N (ng/ml) | Unbound ISF concentration of NPX at 50% maximum inhibition | 221 (Fixed) | 136 (Fixed) |
| Iʹmax,D | Maximum inhibition of DEX on production of paw edema | 1 (Fixed) | 1 (Fixed) |
| ICʹ50,D (ng/ml) | Unbound ISF concentration of DEX at 50% maximum inhibition | 0.62 (Fixed) | 0.39 (Fixed) |
| Drug interaction parameter | |||
| ψ2 | Interaction term for inhibition of paw edema production | 1.16 (28.82) | 0.98 (37.28) |