Table 4.
Parameter estimates for pharmacokinetic (PK) and pharmacodynamic (PD) population parameters, corresponding bootstrap and relative percentage (%) standard errors (SE) of the estimates of the final model
| Parameter estimate | Base model (95% CI) | Covariate model (95% CI)* | Bootstrap (95% CI)† | Relative % SE of the parameter estimate‡ |
|---|---|---|---|---|
| PK model | ||||
| CL (l h−1) | 0.69 | 0.3 renal (0.14, 0.45) | 0.29 (0.13, 0.46) | 27.4 |
| 0.42 non-renal (0.24, 0.61) | 0.42 (0.25, 0.60) | 22.3 | ||
| Vc (l) | 3.46 | 3.43 (2.20, 4.66) | 3.42 (2.07, 5.17) | 18.3 |
| Ka (h) | 0.25 | 0.26 (0.17, 0.35) | 0.26 (0.16, 0.40) | 18.3 |
| Vp (l) | 6.14 | 5.77 (0.75, 10.8) | 6.42 (3.0, 17.8) | 44.3 |
| Q (l h−1) | 0.3 | 0.31 (0.15, 0.47) | 0.28 (0.1, 0.44) | 27.0 |
| ωCL (% CV) | 48.0 | 37.8 (22.3, 48.0) | 37.4 (28.3, 50.9) | 32.2 |
| ωVc (% CV) | 42.5 | 35.6 (7, 51.0) | 34.6 (5.4, 52.9) | 52.9 |
| ωKa (CV%) | 32.7 | 30.3 (5.3, 42.5) | 29.8 (1.7, 49.8) | 49.6 |
| ε (IU ml−1) | 0.1 | 0.09 (0.086, 0.1) | 0.09 (0.083, 0.1) | 14.5 |
| OF | −859.9 | −909.16 | – | – |
| Proportional-odds model (PD) | ||||
| θ1 | 2.83 | 2.83 (1.26, 4.40) | 2.87 (1.26, 4.69) | 28.3 |
| θ2*Age/61 | −2.75 | −2.75 (−4.31, −1.19) | −2.8 (−4.51, −1.13) | 29.0 |
| θ3*cAUC/23 | −0.54 | −0.54 (−0.84, −0.24) | −0.54 (−0.86, −0.21) | 28.7 |
| θ4 | 2.05 | 2.05 (1.47, 2.63) | 2.1 (1.55, 2.80) | 14.4 |
CL, clearance; Vc, central volume of distribution; Ka, absorption rate constant; Vp, peripheral volume of distribution; Q, intercompartmental clearance; ω, between-subject variability; ε, additive residual error; OF, objective function; cAUC, cumulative area under the concentration–time curve; Age (years).
*
Confidence intervals (CI) presented as mean ± standard error ×1.96.
†
Denotes 95% bootstrapped CI (2.5 and 97.5 %ile values).
‡
Calculated as standard error divided by the mean (×100).