Table 2.
Mepolizumab population pharmacokinetic parameter estimates from the final model (primary population pharmacokinetic analysis)
| Mepolizumab population pharmacokinetic parameter estimate (95% CIs) | |||
|---|---|---|---|
| Normalized to 27 kg | Normalized to 50 kg | Normalized to 70 kg (for comparison with adults) | |
| AUC(0‐inf) (μg ⁎ day/mL) | 454.4 (422.1, 486.7) | 675.2 (602.2, 748.2) | 508.2 (423.3, 593.2) |
| C max (μg/mL) | 10.2 (9.5, 10.9) | 16.3 (15.0, 17.6) | 12.8 (11.2, 14.4) |
| C max SS (μg/mL) | 17.8 (15.3, 20.2) | 28.5 (25.0, 31.9) | 22.3 (19.2, 25.5) |
| CL/F (L/day) | 0.09 (0.08, 0.09) | 0.15 (0.13, 0.16) | 0.20 (0.16, 0.23) |
| C av (μg/mL) | 16.2 (15.1, 17.4) | 24.1 (21.5, 26.7) | 18.2 (15.1, 21.2) |
| t ½ (days) | 23.6 (21.9, 25.3) | 21.8 (19.6, 24.1) | 21.0 (17.6, 24.3) |
| KA (per day) | 0.17 (0.13, 0.20) | ||
| Between‐subject variability for CL/F (%) | 15.5 (10.6, 19.3) | ||
| CL allometric exponent | 0.84 (0.65, 1.04) | ||
| V allometric exponent | 0.72 (0.56, 0.88) | ||
| Residual error | 0.029 (0.023, 0.036) | ||
Data are normalized to 27 kg (mean in the <40 kg group receiving 40 mg mepolizumab SC), 50 kg (mean in the ≥40 kg group receiving 100 mg mepolizumab SC), and 70 kg (bodyweight for a typical adult). KA, between‐subject variability, CL, allometric exponent, and V, allometric exponent estimates apply to all subgroups.
AUC(0‐inf), area under the concentration‐time curve from time zero (predose) extrapolated to infinite time; C av, average concentration; CI, confidence interval; CL/F, apparent plasma clearance; C max, maximum plasma concentration; C max SS, maximum plasma concentration at steady state; KA, absorption rate constant; SC, subcutaneous; t ½, half‐life; V, volume of distribution.