Table 5.
Fixed and Random Effects Parameter Estimates for the Risankizumab Population Pharmacokinetic Model Based on Global and Japan Studies
| Parameter | Population Estimate (%RSE)a , b | Bootstrap 95%CI |
|---|---|---|
| Clearance (CL; L/d) | 0.244 (1.8) | 0.218 to 0.265 |
| Central volume of distribution (Vc; L) | 4.87 (3.8) | 4.04 to 5.65 |
| Absorption rate constant (Ka; d‐1) | 0.230 (4.8) | 0.180 to 0.302 |
| Intercompartmental clearance (Q; L/d) | 0.648 (3.7) | 0.529 to 0.784 |
| Peripheral volume of distribution (Vp; L) | 4.25 (2.0) | 3.87 to 4.66 |
| Absolute SC bioavailability (F)c , d | 0.89 (7.2) | 0.796 to 0.970 |
| Exponent for effect of body weight on risankizumab clearance (CL) | 0.935 (3.1) | 0.871 to 0.996 |
| Exponent for effect of body weight on risankizumab central volume of distribution (Vc) | 1.18 (6.9) | 0.976 to 1.36 |
| Exponent for effect of serum albumin on risankizumab clearance (CL) | –0.717 (10.2) | –0.899 to –0.535 |
| Exponent for effect of serum creatinine on risankizumab clearance (CL) | –0.242 (10.1) | –0.294 to –0.189 |
| Exponent for effect of C‐reactive protein on risankizumab clearance (CL) | 0.044 (10.1) | 0.034 to 0.053 |
| Exponent for effect of body weight on risankizumab peripheral volume of distribution (Vp) | 0.360 (12.3) | 0.220 to 0.499 |
| Proportional increase in CL for ADA titer ≥128 | 0.431 (5.0) | 0.292 to 0.757 |
| Variance of interindividual variability in CL, exponential error model | 0.055 | 0.039 to 0.067 |
| Variance of interindividual variability in Vc, exponential error model | 0.111 | 0.053 to 0.154 |
| Variance of interindividual variability in Ka, exponential error model | 0.336 | 0.140 to 0.575 |
| Variance of interindividual variability in Fe; additive error model in logit domain | 0.489 | 0.270 to 0.886 |
| Covariance between IIV CL and IIV Vc, % correlation | 0.031 | ‐0.0004 to 0.051 |
| Variance of proportional residual error | 0.036 | 0.033 to 0.038 |
ADA indicates antidrug antibodies; CL, clearance; F, bioavailability; IIV, interindividual variability; Ka, first‐order absorption rate constant; Q, intercompartmental clearance; SC, subcutaneous; Vc, central volume of distribution; Vp, peripheral volume of distribution.
% Relative standard error (%RSE) was estimated as the standard error of the estimate divided by the population estimate multiplied by 100.
%RSE and 95%CIs are relevant for the updated refined population pharmacokinetic model.
Bioavailability for SC dosing in global phase 3 or Japan phase 2/3 studies.
Estimate was back‐transformed from the logit scale (estimate on the logit scale was 2.09).
The estimates are provided in the logit domain.