TABLE 2.
Summary of pharmacokinetic parameters
| Parameter (unit)a | Base model estimate | Final model estimate | Median bootstrap estimate | %RSEb |
|---|---|---|---|---|
| Absorption | ||||
| F1 | 0.414 | 0.414 | ||
| tlag1 (h) | 1.97 | 1.97 | ||
| Ka (h−1) | 0.504 | 0.504 | ||
| F2 | 0.586 | 0.586 | ||
| tlag2 (h) | 0.445 | 0.445 | ||
| Duration of zero-order absorption (h) | 0.675 | 0.675 | ||
| Disposition | ||||
| CL/F (liters · h−1) (CYP2B6 normal metabolizer; FFM, 56 kg) | 6.36 | 7.52 | 7.56 | 1.70 |
| Vc/F (liters) | 125 | 125 | 127 | 6.03 |
| Vp/F (liters) (FM, 19 kg) | 364 | 374 | 386 | 3.53 |
| Q/F (liters · h−1) | 37.9 | 32.3 | 33.3 | 5.21 |
| CYP2B6 effect on CL/F | ||||
| CYP2B6 normal metabolizer (factor) | 1 | |||
| CYP2B6 reduced metabolizer (factor) | 0.752 | 0.740 | 5.54 | |
| CYP2B6 poor metabolizer (factor) | 0.490 | 0.494 | 7.22 | |
| Between-subject variability (SD) | ||||
| CL/F | 0.366 | 0.257 | 0.257 | 6.85 |
| Vc/F | 0.307 | 0.318 | 0.318 | 7.16 |
| Vp/F | 0.591 | 0.374 | 0.374 | 7.01 |
| Q/F | 0.547 | 0.671 | 0.624 | 15.77 |
| tlag1 | 0.263 | 0.271 | 0.272 | 7.85 |
| Ka | 0.837 | 0.965 | 0.952 | 7.72 |
| tlag2 | 0.480 | 0.473 | 0.472 | 7.53 |
| Duration of zero-order absorption | 0.677 | 0.703 | 0.703 | 6.83 |
| Correlation (ρ)c | ||||
| CL/F to Vp/F | 0.196 | 0.248 | 59.78 | |
| Q/F to Vp/F | 0.849 | 0.831 | 8.27 | |
| Residual error | ||||
| Proportional error (%) | 0.016 | 0.016 | 0.130 | 8.90 |
| Additive error (nmol/liter) | 5,290 | 4,270 | 4,320 | 10.78 |
F, bioavailability; F1, fraction of dose absorbed by first-order absorption; F2, fraction of dose absorbed by zero-order absorption; tlag1, time between dosing event and initiation of first-order absorption from the gut compartment; tlag2, time between dosing event and initiation of zero-order absorption from the gut compartment; duration, duration of time that zero-order absorption occurs following the absorption lag time (tlag2); CL/F, apparent oral plasma clearance; Vc/F, apparent central volume of distribution; Vp/F, apparent peripheral volume of distribution; Q/F, apparent inter-compartmental clearance; CL/F = CLTV × (FFM/56)3/4 × factor (liters · h−1) (for subjects with normal CYP2B6 metabolizer status); Vp/F = Vp,TV × (FM/19) (liters). Proportional error, additive error, and between-subject variation are expressed as standard deviations.
Percent relative standard error (%RSE) was calculated from 1,000 bootstrapped parameter estimates. %RSE = 100 × (bootstrap SE/population model parameter estimate).
The correlations between BSV terms i and j are reported as correlation coefficients, where ρi,j = cov(ωi, ωj)/(ωi × ωj).