Table II.
Population Parameter Estimates for the TMDD Model
| Parameter | Units | Description | Estimate (RSE%) | IIV |
|---|---|---|---|---|
| CLA | L/day | Clearance of antibody | 0.999 (9) | 42.5 (0.08) |
| VC | L | Central volume of distribution | 1.10 (7) | 7.3 (22) |
| VP | L | Peripheral volume of distribution | 5.28 (22) | – |
| Q | L/day | Inter-compartmental clearance | 1.1a | – |
| F | % | Subcutaneous bioavailability | 50a | – |
| kA | Day−1 | Subcutaneous absorption rate | 0.211 (8) | 31.3 (7) |
| CLSR | L/day | Clearance of sIL7Rα | 2.24 (23) | – |
| VR | L | Volume of sIL7Rα | = VC | – |
| CLC1 | L/day | Clearance of the mAb:sIL7Rα complex | 0.196 (21) | – |
| KD1 | nM | Dissociation constant of mAb:sIL7Rα | 0.779 (59) | – |
| BLSR | nM | Baseline concentration of sIL7Rα | 0.45 (14) | 35.1 (0) |
| CLCR | L/day | Clearance of the cIL7Rα | 10.4 (26) | – |
| CLC2 | L/day | Clearance of the mAb:cIL7Rα complex | = CLCR | – |
| KD2 | nM | Dissociation constant of mAb:cIL7Rα | 0.450 (20) | – |
| BLCR | nM | Baseline concentration of cIL7Rα | 1.37 (13) | – |
| Residual error (ε) | ||||
| σ1 | % | Proportional error, PK | 0.434 (6) | – |
| σ2 | % | Additive error, RO | 18.2 (30) | – |
| σ3 | % | Proportional error, sIL7Rα | 0.150 (8) | – |
RSE relative standard error, IIV interindividual variability expressed as % coefficient of variation (% η-shrinkage), sIL7Rα soluble IL7 receptor α, cIL7Rα IL7 receptor α on T cells, mAb monoclonal antibody. Dashes indicate data not computed
aFixed to the typical value estimated from healthy volunteers administered SC or IV PF-06342674