Table 3.
Population pharmacokinetic parameter estimates derived from the base and the final models with their relative standard error (RSE%) and the parameter estimates from 1000 successful bootstrap replicates with 95% confidence interval (CI)
| Base model | Final model | 1000 bootstrap runs | ||||
|---|---|---|---|---|---|---|
| Parameter | Mean | RSE % | Mean | RSE % | Mean | 95% CI* |
| Fixed effects | ||||||
| CL (l h−1) | 11.3 | 33 | 6.42 (14.74†/5.51‡) | 34 | 6.93 | 3.64, 12.8 |
| Q (l h−1) | 3.93 | 47 | 3.74 | 46 | 3.89 | 1.66, 7.21 |
| V1 (l) | 7.86 | 55 | 7.24 | 55 | 8.20 | 2.90, 18.5 |
| V2 (l) | 18.10 | 54 | 16.80 | 52 | 17.8 | 5.79, 34.9 |
| ka (h−1) | 0.33 | 20 | 0.39 | 20 | 0.42 | 0.27, 0.71 |
| F | 0.64 | 36 | 0.48 | 32 | 0.50 | 0.27, 0.82 |
| Weight factor | – | – | 1.09 | 30 | 1.06 | 0.42, 1.80 |
| Concomitant ciclosporin factor | – | – | −0.60 | 10 | −0.61 | −0.73, −0.48 |
| Interindividual variability | ||||||
| ωCL (CV%) | 54.3 | 24 | 31.6 | 26 | 30.0 | 20.8, 38.3 |
| ωQ (CV%) | – | – | – | – | – | – |
| ωV1 (CV%) | – | – | – | – | – | – |
| ωV2 (CV%) | – | – | – | – | – | – |
| ωka (CV%) | 61.1 | 87 | 59.1 | 79 | 57.0 | 9.5, 116.6 |
| ωF (CV%) | 49.0 | 54 | 34.6 | 59 | 33.0 | 10.2, 58.7 |
| Interoccasion variability | ||||||
| πCL (CV%) | 5.9 | 112 | 5.8 | 105 | 5.0 | 0.1, 9.1 |
| πV1 (CV%) | – | – | – | – | – | – |
| Random residual variability | ||||||
| σ1 | 0.48 | 14 | 0.48 | 14 | 0.47 | 0.40, 0.53 |
RSE, relative standard error; CL, clearance; Q, inter-compartmental clearance; V1 volume of distribution in central compartment; V2 volume of distribution in peripheral compartment; ka absorption rate constant; F bioavailability; σ1 residual variability.
*
Percentile bootstrap 95% CI corresponding to parameter estimates at the 2.5th and 97.5th percentiles of bootstrap runs.
†
Concomitant ciclosporin
‡
Concomitant tacrolimus.