Table 1.
Parameter estimates of the population PK model after completion of cohort 5.
| Model parametersa | Interpretation | Typical values (median) | Inter-individual variability (variance) |
|---|---|---|---|
| Vmax (pg/mL/h) | Maximum elimination rate of the Michaelis-Menten nonlinear clearance pathway | 0.418 | Fixed to 0 |
| Km (pg/mL) | Michaelis-Menten constant of the nonlinear clearance mechanism | 76.1 | 215% |
| CL (L/h) | Linear clearance | Fixed to 0 | Fixed to 0 |
| V1 (L) | Distributional volume in central compartment | 11.7 | 16% |
| V2 (L) | Distributional volume in peripheral compartment | 3.86 | 3.7% |
| Q (L/h) | Inter-compartmental clearance | 0.383 | 35% |
| Ka (h−1) | First-order absorption rate constant | 0.67 | 142% |
| Ε | Residual error | 44%b | Fixed to 0 |
Note: No relative standard error of model parameters was estimated and bioavailability was not estimated since no intravenous data were available. Inter-individual variability of parameters (η) and residual error (ε) were assumed normally distributed with mean 0 and variance Ω2 and σ2 respectively. Variances are expressed as coefficient of variation (%).
a
Estimates based on 17 patients and 289 PK observations after oral administration of IMP up to cohort 5.
b
Residual error was estimated on a coefficient of variation scale (%).