Table 3.
Parameter | Estimate | RSE (%) | Shrinkage (%) |
---|---|---|---|
Fixed effects | |||
Vm (mg/day) | 8.06 | 1.96 | N/A |
Km (mg/L) | 0.939 | 4.38 | N/A |
Vc/F (L) | 2.08 | 3.20 | N/A |
CLO/F (L/day) | 0.260 | 5.36 | N/A |
Ka (day) | 0.136 | 2.53 | N/A |
Q/F (L/day) | 0.156 | 3.87 | N/A |
Vp/F (L) | 5.23 | 5.98 | N/A |
WT effect on CLO/F | 0.885 | 12.0 | N/A |
WT effect on Vm | 0.516 | 9.45 | N/A |
ALBR effect on Vm | − 0.844 | 5.49 | N/A |
CrCl effect on Vm | 0.212 | 9.59 | N/A |
DP2 effect on Ka | 0.663 | 4.38 | N/A |
ADA effect on CLO/F | 1.43 | 3.05 | N/A |
DP2 effect on CLO/F | 1.30 | 4.48 | N/A |
Sex effect on CLO/F | 0.846 | 4.74 | N/A |
BLCRP effect on Vm | 0.0299 | 23.0 | N/A |
Inter-individual variability (CV%) | |||
Vma | 32.4 | 6.07 | 29.8 |
CLO/Fa | 55.3 | 6.21 | 42.8 |
Vc/Fa | 37.3 | 16.7 | 64.2 |
Kaa | 32.1 | 9.52 | 49.6 |
Block Vm-CLO/Fb | − 0.566 | 10.8 | N/A |
Residual variability (CV%) | |||
σ2c | 0.395 | 0.811 | N/A |
ADA anti-drug antibody, ALBR albumin normalized to upper limit of normal, BLCRP baseline C-reactive protein, CLO/F apparent linear clearance from central compartment, CrCl body-surface-area-normalized creatinine clearance, DP2 sarilumab drug product, Ka absorption rate constant, Km Michaelis–Menten constant, N/A not applicable, Q/F apparent inter-compartmental clearance, RSE (%) percentage of relative standard error (100 × standard error/estimate), Vc/F apparent volume of central compartment, Vm maximum elimination rate, Vp/F apparent peripheral volume of distribution, WT body weight
aInter-individual variability is expressed as % coefficient of variation (CV%)
bEstimate of covariance between two variances is expressed as a correlation coefficient
cVariance of residual error is based on the log-transformed dependent variable (i.e., sarilumab concentration)