Table 3.
Final population covariate model parameter estimates
| Estimate (%SEP)* | Asymptotic(95% CI)† | Bootstrap median (95% CI) | |
|---|---|---|---|
| PK parameters; typical values | |||
| Clearance, CL (l h−1) | 0.164 (11.6) | (0.127, 0.201) | 0.166 (0.138, 0.25) |
| Central compartment volume, V1 (l) | 5.98 (13.7) | (4.37, 7.59) | 6.13 (4.96, 10.2) |
| Peripheral compartment volume, V2 (l) | 1.21 (40.4)‡ | 0.252, 2.17) | 1.22 (0.721, 28.2) |
| Central to peripheral compartment clearance, Q (l h−1) | 0.0153 (38.1)‡ | (0.00387, 0.0267) | 0.0192 (0.013, 0.0396) |
| First-order absorption rate constant, Ka (h−1) | 0.0212 (3.54) | (0.0197, 0.0227) | 0.0211 (0.0194, 0.0225) |
| Bioavailability equation: F = F0 + p1 × Dose | |||
| F0 | 0.448 (10.2)‡ | (0.358, 0.538) | 0.450 (0.389, 0.702) |
| p1 | 0.000586 (37.2)‡ | (0.000159, 0.00101) | 0.000576 (0.000225, 0.00109) |
| eEPO concentration (ng ml−1) | 0.0867 (4.19) | (0.0796, 0.0938) | 0.0872 (0.0795, 0.0958) |
| Covariate coefficients | |||
| r1 (BWT on CL) | 1.19 (21.9) | (0.678, 1.70) | 1.19 (0.668, 1.74) |
| r2 (BWT on V1) | 0.983 (44.9) | (0.119, 1.85) | 1.01 (0.0572, 1.93) |
| r3 (Age on Ka) | −0.951 (7.48) | (−1.09, −0.812) | −0.953 (−1.12, −0.823) |
| Interindividual variances | Estimate (%SEP) | ∼ CV%§ | Asymptotic (95% CI) | Bootstrap median (95% CI) |
|---|---|---|---|---|
| ωCL2 | 0.075 (25.3) | 27.4 | (0.0378, 0.112) | 0.0707 (0.0398, 0.112) |
| ωV12 | 0.227 (20.1) | 47.6 | (0.137, 0.317) | 0.215 (0.136, 0.32) |
| ωKa2 | 0.0832 (24.2) | 28.8 | (0.0438, 0.123) | 0.0785 (0.0413, 0.117) |
| ωeEPO2 | 0.132 (28.5) | 36.3 | (0.0583, 0.206) | 0.122 (0.0524, 0.222) |
| σ12, RRV | 0.324 (3.64)¶ | 56.9 | (0.301, 0.347) | 0.323 (0.299, 0.345) |
*
%SEP, Standard error of parameter estimate defined as the standard error of prediction/predicted value × 100% (measure of uncertainty in the parameter estimate).
†
Asymptotic 95% CI is calculated as parameter estimates ± 1.96 × standard error of prediction.
‡
Interindividual random variance was fixed at 0 in the PK model.
§
Approximate CV% is calculated as the square root of the variances.
¶
σ1 is assumed to have mean 0. BWT, Body weight; CI, confidence interval; CV, coefficient of variation; RRV, random residual variability; eEPO, endogenous erythropoietin.