Table 4.
Final model parameter estimates of the original population pharmacokinetic (POPPK) model developed by Svensson et al. (2018a) compared to final parameter estimates of the re-estimated POPPK model without inter-occasion variability (IOV).
| Parameter | Description | Estimates original model | Estimates model without IOV (RSE [%]) |
|---|---|---|---|
| Vmax (mg/h/70 kg) | Maximal elimination rate | 525 | 309.8 (19.9%) |
| km (mg/L) | Concentration at which half of the elimination is reached | 35.3 | 15.8 (19.5%) |
| V (L/70 kg) | Volume of distribution | 87.2 | 93.6 (8.0%) |
| ka (h−1) | Absorption rate constant | 1.77 | 2.4 (43.2%) |
| MTT (h) | Mean transit time | 0.51 | 0.81 (16.0%) |
| NN | Number of transit compartments | 23.8 | 7.6 (25.7%) |
| Emax | Maximal increase in enzyme production rate | 1.16 | 1.2 (11.6%) |
| EC50 (mg/L) | Concentration at which half Emax is reached | 0.0699 | 0.053 (125.6%) |
| kENZ (h−1) | First-order rate constant for enzyme degradation and formation | 0.00603 | 0.0053 (25.0%) |
| Fmax | Maximal increase in bioavailability with doses above 450 mg | 0.504 | 0.40 (33.9%) |
| ED50 (mg) | The dose at which half Fmax is reached | 67.0 | 17.4 (374.4%) |
| IIV Vmax (%) | Inter-individual variability in Vmax | 30.0 | 55.2 (17.7%) |
| IIV km (%) | Inter-individual variability in km | 35.8 | 80.6 (13.8%) |
| IIV V (%) | Inter-individual variability in V | 7.86 | 8.6 (64.4%) |
| IIV ka (%) | Inter-individual variability in ka | 33.8 | 28.7 (174.8%) |
| IIV MTT (%) | Inter-individual variability in MTT | 38.2 | 58.8 (18.8%) |
| IIV NN (%) | Inter-individual variability in NN | 77.9 | 90.5 (18.3%) |
| IOV km (%) | Inter-occasion variability in km | 18.9 | 0 FIX |
| IOV ka (%) | Inter-occasion variability in ka | 31.4 | 0 FIX |
| IOV MTT (%) | Inter-occasion variability in MTT | 56.4 | 0 FIX |
| IOV F (%) | Inter-occasion variability in F | 15.7 | 0 FIX |
| Correlation Vmax-Km (%) | 38.9 | 59.6 (15.9%) | |
| (%) Additive error on log scale | 23.6 | 56.9 (0.9%) |
IOV, inter-occasion variability; RSE, relative standard error reported on the approximate standard deviation scale.