Table II.
Pharmacodynamic Parameter Estimates for DEX Efficacy for Paw Edema in CIA Rats
| Parameters (units) | Definition | Females | Males | ||
|---|---|---|---|---|---|
| Estimate (%RSE) | IIV (%RSE) | Estimate (%RSE) | IIV (%RSE) | ||
| Disease-specific | |||||
| tonset (h) | Time of disease onset | 256 (0.4) | NA | 300 (0.6) | NA |
| kout (1/h) | Loss of edema rate constant | 0.0088 (8.2) | NA | 0.0088 (8.2) | NA |
| kdeg (1/h) | Loss of production rate constant | 0.00099 (8.4) | NA | 0.00047 (18.1) | NA |
| kg (1/h) | Natural growth rate constant | 0.00101 (20.4) | NA | 0.00101 (20.4) | NA |
| Pawss (mm2) | Paw size at steady-state | 73.1 (5.3) | NA | 108 (7.4) | NA |
| Paw0 (mm2) | Paw size on day 0 | 57.1 (1.0) | 13.2 (6.3) | 78.1 (0.8) | 13.2 (6.3) |
| (mm2/h) | Disease production rate constant at tonset | 1.66 (4.8) | 10.7 (4.3) | 1.66 (4.8) | 10.7 (4.3) |
| ε (%) | RV (prop) | 0.59 (6.3) | 0.59 (6.3) | ||
| Drug-specific | |||||
| Imax | Maximum inhibition | 1 (Fixed) | NA | 1 (Fixed) | NA |
| IC50 (ng/mL) | Unbound ISF DEX concentration at 50% Imax | 0.101 (60.4) | NA | 0.0146 (135.6) | NA |