Table 3.
Model parameters estimated for the final model
| Fixed-effect parameters | Estimate | RSE (%) | Untransformed parameter | |
|---|---|---|---|---|
| Absorption rate constant (log K a) | −1.09 | 8 | 0.34/h ~ t 1/2 = 124 min | |
| Systemic clearance (log CL) | 0.62 | 7 | 1.86 L/h | |
| Central volume of distribution (log V 2) | 2.62 | 4 | 13.7 L | |
| Absolute bioavailability (log F) | −0.55 | 9 | 58% | |
| First inter-compartmental clearance (log Q3) | 1.65 | 7 | 5.18 L/h | |
| Volume of the first peripheral compartment (log V 3) | 5.73 | 1 | 309 L | |
| Second inter-compartmental clearance (log Q4) | 3.26 | 2 | 26.1 L/h | |
| Volume of the second peripheral compartment (log V 4) | 5.32 | 1 | 205 L | |
| Absorption lag time (log T LAG) | −1.52 | 0 | 13 min | |
| Impact of BSA on V 4 (V 4[BSA]) | 2.06 | 18 | −37 and +46% at the 5th and 95th percentile (1.5 and 2.25 m2) on V 4 relative to median BSA (1.87 m2) |
| Random-effect parameters | Estimate | RSE* (%) | η shrinkage (%) | |
|---|---|---|---|---|
| Inter-individual variability on log CL | 44% | 11 | 21 | |
| Inter-individual variability on log F | 73% | 8 | 13 | |
| Correlation between log CL and log F | 82% | 11 | ||
| Inter-individual variability on log V 4 | 79% | 12 | 37 | |
| Initial sd of the residual error (SD1) | 1.90 | 11 | ||
| Steady state sd of the residual error (SD0) | 0.46 | 3 | ||
| Time constant of residual error sd (K SD) | 0.84 | 22 | t 1/2 = 50 min | |
| Residual random variability | 7 |
Inter-individual variability shown as % coefficient of variation. *rse inter-individual variability is derived as 100%·se ω2/ω 2
Model parameters and RSEs correspond to the raw estimates provided by NONMEM. The untransformed parameters show the corresponding pharmacokinetic parameters
BSA body surface area, CL systemic clearance, F bioavailability, K SD rate constant of change in SD, Q 3 first inter-compartmental clearance, Q 4 second inter-compartmental clearance, RSE relative standard error, sd standard deviation, SD 0 asymptotic standard deviation, SD 1 standard deviation at the beginning of the treatment period, T LAG absorption lag time, V 2 central volume of distribution, V 3 volume of distribution of first peripheral compartment, V 4 volume of distribution of second peripheral compartment