Table 5.
Pharmacokinetic parameter estimates for the base and final updated models
| Parameter | Base model (Model 5) | Final updated model (Model 9) | ||
|---|---|---|---|---|
| Estimate | 90% CI | Estimate | 90% CI | |
| CL, L/day | 0.357 | 0.341–0.374 | 0.291 | 0.28–0.302 |
| Body weight on CL, power | 0.807 | 0.751–0.864 | ||
| ADAs on CL, fraction | 2.24 | 2.18–2.3 | ||
| Vc, L | 3.82 | 3.56–4.10 | 3.13 | 2.97–3.31 |
| Body weight on Vc, power | 0.803 | 0.627–0.979 | ||
| Q, L/day | 1.46 | 0.899–2.38 | 0.738 | 0.679–0.803 |
| Body weight on Q, power | 0 | – | ||
| Vp, L | 2.77 | 2.49–3.09 | 2.52 | 2.34–2.71 |
| Body weight on Vp, power | 0.528 | 0.351–0.706 | ||
| ka, half-life; days | 3.35 | 2.76–4.07 | 3.54 | 3.15–3.99 |
| F | 0.671 | 0.637–0.707 | 0.589 | 0.565–0.614 |
| Change in F with study CP220, fraction | 0.569 | 0.521–0.622 | 0.490 | 0.461–0.522 |
| IIV | ||||
| ηCL, %CV | 29.5 | 27.6–31.3 | 24.2 | 22.6–25.6 |
| ηVc, %CV | 29.9 | 24.6–34.5 | 24.4 | 20.7–27.6 |
| ηQ, %CV | 132 | 101–157 | 8.94 | – |
| ηVp, %CV | 37.3 | 29.6–43.6 | 44.7 | 40.5–48.5 |
| ηka (half-life), %CV | 68.1 | 57.6–77.2 | 83.1 | 75.5–90.1 |
| ηF, %CV | 11.9 | 4.19–16.3 | 17.1 | 13.5–20 |
| ηF (study CP220), %CV | 61.6 | 53.4–68.7 | 35.0 | 28.8–40.2 |
| Residual variability | ||||
| Proportional error, %CV | 28.1 | 26.5–29.7 | 25.0 | 23.8–26.1 |
| Proportional error (study CP220), %CV | 57.9 | 55.5–60.1 | 54.5 | 52.5–56.3 |
| Proportional error (studies SIROCCO, CALIMA, ZONDAa, BISE), %CV | 46.0 | 45.4–46.7 | 36.7 | 36.2–37.1 |
ADAs antidrug antibodies, CI confidence interval, CL clearance, CV coefficient of variation, F bioavailability, IIV interindividual variability, ka absorption rate constant, Q intercompartmental clearance, Vc central volume of distribution, Vp peripheral volume of distribution
aZONDA was not included in the base model