Table 2. The median values of the PK parameter estimates of VPA in the final population PK models obtained using the NONMEM program and the bootstrap analysis.
| Parameter | NONMEM | Bootstrap Evaluation | |
| Final Estimates | Median | 95% CIs | |
| ALAG (h) | 3.00 (Fixed) | – | – |
| Ka (h−1) | 0.109 | 0.104 | 0.0317–0.748 |
| Vd/F (L) | 21.4 | 21.2 | 8.01–68.1 |
| CL/F (L/h) | 0.559 | 0.558 | 0.520–0.589 |
| Dose on Vd/F (L) | 1.52 | 1.46 | 0.457–3.74 |
| Dose on CL/F (L/h) | 0.596 | 0.592 | 0.525–0.652 |
| Gender on CL/F (L/h) | 0.917 | 0.915 | 0.847–0.998 |
| CBZ on CL/F (L/h) | 1.19 | 1.20 | 1.13–1.29 |
| CLB on CL/F (L/h) | 0.906 | 0.907 | 0.852–0.970 |
| PB on CL/F (L/h) | 1.12 | 1.12 | 1.03–1.24 |
| PHT on CL/F (L/h) | 1.43 | 1.43 | 1.31–1.56 |
| ω2 on ALAG | 4.48×10−9 | 6.69×10−5 | 6.69×10−5–6.69×10−5 |
| ω2 on Ka | 7.77×10−7 | 8.82×10−4 | 8.81×10−4–8.82×10−4 |
| ω2 on Vd/F | 1.83×10−7 | 4.28×10−4 | 4.28×10−4–4.28×10−4 |
| ω2 on CL/F | 0.0587 | 0.241 | 0.202–0.281 |
| σ2 (proportional error) | 0.0617 | 0.247 | 0.224–0.268 |
VPA = valproic acid; PK = pharmacokinetic; NONMEM = nonlinear mixed-effect model; CIs = confidence intervals; ALAG = absorption lag time; Ka = absorption rate constant; Vd/F = volume of distribution; CL/F = apparent oral clearance; Dose = daily dose of VPA; CBZ = carbamazepine; CLB = clobazam; GBP = gabapentine; PB = phenobarbital; PHT = phenytoin; ω = coefficient of variation of inter-individual variability; σ = coefficient of variation of intra-individual variability; – = data not available.