Table 2.
Parameter estimates obtained by fitting the equilibrium model to total antibody and total ligand data
| Parameter description | Population estimate (%SEE) | Actual | ||
| Scenario 1 | Scenario 2 | Scenario 3 | ||
| ka (hr−1) | 0.0125 (10.0) | 0.0110 (8.81) | 0.0103 (7.52) | 0.00837 |
| CL/F (L hr−1 kg−1) | 0.00216 (8.70) | 0.00216 (8.43) | 0.00215 (8.14) | 0.00193 |
| V/F (L kg−1) | 0.364 (6.79) | 0.321 (6.73) | 0.294 (7.93) | 0.231 |
| kin (nM hr−1) | 0.0810 (13.3) | 0.239 (6.78) | 0.368 (4.40) | 0.417 |
| kout (hr−1) | 1.45 (11.9) | 3.86 (6.89) | 5.58 (6.68) | 6.85 |
| KD (nM) | 0.179 (17.1) | 0.0572 (14.0) | 0.0373 (12.0) | 0.03a |
| Variability | ||||
| IIV in CL/F | 31.9% (29.8) | 27.8% (28.0) | 26.7% (26.8) | 28.3% |
| IIV in kout | 0 (FIXED) | 0 (FIXED) | 0 (FIXED) | 12.7% |
| Res_prop for PK | 36.5% (16.2) | 35.4% (15.1) | 34.9% (15.1) | 31.6% |
| Res_prop for PD | 48.8% (6.89) | 33.5% (7.61) | 20.5% (8.55) | 17.3% |
SEE, Standard error of the estimate; IIV, Inter-individual variability; Res_prop, Proportional residual error.
a
Simulated dataset did not utilize KD, but rather micro-constants that gave a KD of 0.03 nM. kon and koff were 0.042 nM−1 hr−1 and 0.0013 hr−1; 0.42 nM−1 hr−1 and 0.013 hr−1; and 4.2 nM−1 hr−1 and 0.13 hr−1 for scenarios 1, 2 and 3, respectively.