Table 2.
Population PK model final parameter estimates
| Mean | SE | %CV | η-shrinkage (%) | Bootstrap, median (95% CI) | |
|---|---|---|---|---|---|
| CL (L/h/70 kg) | 16.7 | 1.07 | — | — | 16.7 (14.7, 18.9) |
| θ_creatinine | −0.40 | 0.094 | — | — | −0.40 (−0.58, −0.21) |
| V (L/70 kg) | 38.6 | 2.15 | — | — | 38.6 (34.9, 43.4) |
| CLCSF (L/h/70 kg) | 0.017 | 0.004 | — | — | 0.016 (0.001, 0.030) |
| CSF uptakea | 2.39 | 0.205 | — | — | 2.38 (2.01, 2.82) |
| θ_CSF proteinsa | −0.17 | 0.110 | — | — | −0.17 (−0.43, 0.015) |
| IIV on CL | 0.255 | 0.058 | 50.5 | 13.5 | 0.248 (0.154, 0.370) |
| IIV on V | 0.153 | 0.059 | 39.1 | 31.0 | 0.154 (0.042, 0.282) |
| Cov IIV CL-V | 0.167 | 0.055 | — | — | 0.163 (0.070, 0.277) |
| RUV_plasma | 0.679 | 0.108 | — | — | 0.664 (0.489, 0.900) |
| RUV_CSF | 1.19 | 0.125 | — | — | 1.15 (0.941, 1.391) |
| Lambda_plasma | 0.280 | 0.107 | — | — | 0.275 (0.064, 0.482) |
| Lambda_CSF | 0.285 | 0.107 | — | — | 0.279 (0.066, 0.485) |
| Delta_plasma | −0.174 | 0.052 | — | — | −0.178 (−0.287, −0.063) |
SE, standard error from NONMEM covariance step; CV, coefficient of variation; IIV, between-subject variability; Cov, covariance; RUV, residual error; θ, estimated covariate effect.
Lambda and delta are parameters from the dynamic-transform-both-side approach for residual error modelling (more specifically, lambda is the shape parameter and delta is the scedasticity parameter; together they are a part of the Box–Cox power parameter, zeta = lambda + delta).
a
Indicates that the value is on the logit scale.