Table 2.
Parameter estimates from the final PK model and bootstrap analysis
| Parameters | Final estimates | Shrinkage (%) | Bootstrap estimates† | |
|---|---|---|---|---|
| Median | 95% CI | |||
| CL/F (l·h−1·70 kg−1)* | ||||
| CL/F = θ1 * (body weight/70)θ2 | ||||
| θ1 | 22.0 | 21.5 | 14.8, 25.2 | |
| θ2 | 0.31 | 0.31 | 0.03, 0.63 | |
| Vc/F (l) | 45.4 | 43.3 | 29.6, 55.6 | |
| Q/F (l·h−1) | 22.4 | 23.1 | 16.0, 32.5 | |
| Vp/F (l) | 411 | 410.6 | 152.6, 1472.6 | |
| Ka (h−1) | 2.5 | 2.7 | 1.45, 4.93 | |
| MTT (h) | 0.25 | 0.25 | 0.12, 0.50 | |
| Number of transit compartment (n) | 8 fix | – | – | |
| Relative biovailability | ||||
| BIO = θ3 * (DBSA/450)θ4 | ||||
| θ3 | 1 fix | – | – | |
| θ4 | −0.43 | −0.44 | −1.00, −0.06 | |
| Inter-individual variability (%CV)‡ | ||||
| ω (CL/F) | 25.9 | 15% | 24.8 | 8.1, 38.5 |
| ω (Vc/F) | 0 fix | – | – | |
| ω (Q/F) | 0 fix | – | – | |
| ω (Vp/F) | 0 fix | – | – | |
| ω (Ka) | 299.6 | 29% | 288.4 | 123.6, 910.8 |
| ω (MTT) | 144.8 | 34% | 148.5 | 69.4, 414.1 |
| ω (n) | 0 fix | – | – | |
| Additive residual error (%CV)c | ||||
| σadditive | 51.0 | 10% | 50.0 | 43.5, 57.1 |
Apparent clearance is normalized by a reference body weight of 70 kg.
Obtained from 285 out of 300 non-parametric bootstrap runs.
Reported as %CV, calculated by the equation 100*SQRT(exp(ωn) − 1) where ωn is the nonmem output for the inter-subject variability of the nth parameter.
Calculated by the equation 100 × SQRT(σ), where σ is the nonmem output for the variance of the additive residual error. %CV, coefficient of variation; BIO, relative bioavailability; CI, confidence interval; CL/F, apparent clearance; DBSA, dose per body surface area; Ka, absorption rate constant; MTT, mean transit time; Q/F, apparent compartmental clearance between Vc/F and Vp/F; Vc/F, apparent central volume of distribution; Vp/F, apparent peripheral volume of distribution; WT, total body weight.