Table 4.
Parameter values for the final population pharmacokinetic model of vortioxetine in healthy individuals
| Model parameters | Parameter estimate |
|---|---|
| Absorption rate constant (ka) | |
| Estimate (1/hr) | 0.142 |
| RSE1 (%) | 2.7 |
| IIV2 (%) | 51 |
| RSE1 (%) | 7.0 |
| Volume of distribution, central comp (V2/F) | |
| Estimate (L) | 1.97 × 103 |
| RSE1 (%) | 1.6 |
| IIV2 (%) | 31 |
| RSE1 (%) | 7.7 |
| Height on V2/F (L/cm) | 17.4 |
| RSE1 (%) | 12 |
| Oral clearance (CL/F) | |
| Estimate (L/hr) | 52.9 (UM4), 34.1 (EM4), 26.6 (IM4), 18.1 (PM4) |
| RSE1 (%) | 6.0 (UM4), 1.7 (EM4), 2.5 (IM4), 6.6 (PM4) |
| IIV2 (%) | 42 |
| RSE1 (%) | 7.0 |
| Correlation CL/F – V2/F | 0.61 |
| Age on CL/F (L/hr/yr) | 0.277 |
| RSE1 (%) | 8.6 |
| Volume of distribution, peripheral comp (V3/F) | |
| Estimate (L) | 6.61 × 102 |
| RSE1 (%) | 3.8 |
| IIV2 (%) | – |
| Intercompartmental clearance (Q/F) | |
| Estimate (L/hr) | 22.5 |
| RSE1 (%) | 4.6 |
| IIV2 (%) | – |
| Lag-time (ALAG) | |
| Estimate (hr) | 0.781 |
| RSE1 (%) | 0.8 |
| IIV2 (%) | – |
| Residual error | |
| Estimate | 0.0654 |
| Estimate3 (%) | 26 |
| RSE1 (%) | 4.4 |
UM, ultra metaboliser; EM, extensive metaboliser; IM, intermediate metaboliser; PM, poor metaboliser.
1
Relative standard error (RSE) was calculated as Standard Error/Estimate*100 from NONMEM® results.
2
Interindividual variability.
3
Percentage standard deviation calculated as 100*sqrt(Estimate).
4
CYP2D6-inferred metabolic status.