Table 4.
Stages of the model-building process to reach the final pharmacokinetic model of melatonin in the combined dataset
| Parameter | Base model (WT-power allometric; full covariance matrix) | Reduced base model (shared variance model) | Intermediate model (Gender-prop on V) | Final model (Gender-prop on V; Race-exp on CL and V) |
|---|---|---|---|---|
| Observations | 46 | 46 | 46 | 46 |
| Patients | 16 | 16 | 16 | 16 |
| MOFV | 381.97 | 381.97 | 378.05 | 360.91 |
| P value | – | – | 0.047* | 3.48 × 10−5* |
| CL (l h−1) | 0.02 | 0.020 (0.39) | 0.021 (0.37) | 0.021 (0.63) |
| V (l) | 0.75 | 0.75 (0.14) | 0.64 (0.14) | 0.74 (0.08) |
| t1/2 (h) | 26.10 | 26.10 | 21.10 | 24.30 |
| θgender | – | – | 0.47 (0.67) | 1.73 (0.20) |
| θrace | – | – | – | 1.09 (0.13) |
| ωCL (CV%) | 111.80 | 111.90 (0.47) | 103.0 (0.48) | 111.90 (0.75) |
| CorrCL,V | 0.999 | – | – | – |
| ωV (CV%) | 51.70 | – | – | – |
| θCorr | – | 0.46 (0.26) | 0.47 (0.26) | 0.215 (0.57) |
| σprop (CV%) | 24.90 | 24.90 (0.29) | 24.40 (0.30) | 22.90 (0.29) |
Parameters are presented as mean parameter estimate (CV% in the estimate). MOFV: Minimum value of objective function; ΔMOFV indicates a change in MOFV relative to the previous model; *ΔMOFV of −3.84 is significant at P < 0.05 (1 d.f.). Weight (WT) is scaled to a median of 0.867 kg; θrace: fractional difference from θCL and θV at a certain value of Race; θgender: fractional difference from θV at a certain gender value; ω: Inter-individual variability; CorrCL,V: correlation between CL and V variability parameters; θCorr: shared variance between CL and V; σ: residual variability.