Table 2.
Parameter values estimated by the final pharmacokinetic model
| Parameter | Population mean | %RSE* | 95% confidence interval* |
|---|---|---|---|
| Typical apparent clearance, fast eliminators (CLfast/F, l h−1) | 21.6 | 36.8 | 18.9, 28.2 |
| Typical apparent clearance, slow eliminators (CLslow/F, l h−1) | 9.70 | 3.05 | 9.61, 10.7 |
| Typical apparent central volume of distribution (Vc/F, l) | 57.7 | 2.81 | 56.3, 62.9 |
| Typical apparent peripheral volume of distribution (Vp/F, l) | 1730 | 14.7 | 1313, 2514 |
| Typical apparent intercompartmental clearance (Q/F, l h−1) | 3.34 | 8.52 | 2.43, 3.38 |
| Typical absorption rate constant (ka, h−1) | 1.85 | 4.01 | 1.72, 2.06 |
| Typical absorption lag time (tlag, h) | 0.180 | 7.63 | 0.166, 0.226 |
| Proportion of fast eliminators in population (Pfast) | 0.132 | 23.2 | 0.0685, 0.184 |
| Linear effect of positive HIV status on CL/F (θCL,HIV) | −0.174 | 22.2 | −0.266, −0.0990 |
| Linear effect of being female on Vc/F (θVc,gender,F) | −0.103 | 25.7 | −0.205, −0.0861 |
| Interindividual variability (%CV) | |||
| Apparent clearance (ωCL2) | 18.4 | 13.6 | 13.6, 19.3 |
| Apparent central volume of distribution (ωVc2) | 16.5 | 12.6 | 12.4, 16.8 |
| Apparent intercompartmental clearance (ωQ2) | 93.1 | 25.4 | 92.1, 132 |
| Relative bioavailability (ωF2) | 26.2 | 9.77 | 25.2, 29.9 |
| Absorption lag time (ωtlag2) | 88.4 | 9.57 | 86.6, 102 |
| Interoccasional variability (%CV) | |||
| Absorption rate constant (κka2) | 90.1 | 5.92 | 80.5, 92.0 |
| Relative bioavailability (κF2) | 8.4 | 33.0 | 8.77, 14.4 |
| Residual variability (standard deviation) | |||
| Additive variability for DPM (σ, log scale, mg l−1) | 0.205 | 2.74 | 0.187–0.229 |
*
Generated by nonparametric bootstrap, n = 1000. RSE = relative standard error. Typical value of CL/F = CL · (body weight/70)0.75· (1–0.174 · HIV), where CL = 21.6 or 9.70 for fast and slow eliminators, respectively, and HIV = 0 or 1 for negative and positive status, respectively; typical value of Vc/F = 57.7 · (body weight/70) · (1–0.103 · SEX), where SEX is 0 for males and 1 for females; typical value of Vp/F = 1730 · (body weight/70); typical value of Q/F = 3.34 · (body weight/70)0.75.