Table 4. Population pharmacokinetic model parameters for the tipifarnib: combined data set.
| Pharmacokinetic | Typical value | Ratio healthy subjects : | Between subjects | Variability(h) Within | |
|---|---|---|---|---|---|
| parameter | Cancer subjects* | Healthy subjects | cancer subjects* | (IIV,%)* | subjects (IOV,%)* |
| CL (l h−1)(a) | 21.9 (4.11) | 26.5 | 1.21 (6.06) | 24.9 (20.2) | 11.9 (35.3) |
| V2 (l 70 kg−1) | 54.9 (7.61) | 30.0 | 0.55 (31.8) | 20.3 (78.5) | – |
| Q3 (l h−1) | 4.11 (8.37) | 4.11 | – | 74.0 (30.7) | 51.0 (27.6) |
| V3 (l) | 92.4 (9.69) | 92.4 | – | 81.4 c | – |
| Q4 (l h−1) | 14.8 (18.6) | 131 | 8.83 (35.7) | 35.9d | – |
| V4 (l) | 21.4 (13.6) | 56.9 | 2.66 (20.7) | 24.3 e | – |
| D1 (h) | 1.20(i) (3.00) | 1.20 | – | 52.7 (30.1) | 72.7 (18.3) |
| KA (h−1) | 0.71j (7.41) | 1.63 | 2.31 (16.1) | 86.1 (24.4) | 71.8 (21.3) |
| Fabs (%) | 26.7 (4.23) | 26.7 | – | 0.74 (9.78)g | 0.32 (26.2)g |
| tlag (h)(b,k) | 1.24f,g | 2.32 (40.7)g | |||
| Subpopulation 1 | 0.11 (16.7) | 0.11 | – | ||
| Subpopulation 2 | 0.24 (14.1) | 0.24 | |||
Results expressed as parameter (RSE: relative standard error of parameter estimate,%).
Clearance normalized for a bilirubin of 9 µmol l−1. The normalization coefficient is equal to (TBIL/9)θ1, where TBIL is bilirubin (expressed as µmol l−1), and θ1 is −0.103 (RSE = 27.0%).
Proportion of patients in subpopulation 1 is 71.7 (RSE = 36.3%).
Correlation between IIV of Q3 and V3 set to 1. Expansion factor of V3 is 1.21 (RSE = 8.93%).
Correlation between IIV of CL and Q4 set to 1. Expansion factor of Q4 is 2.08 (RSE = 30.6%).
Correlation between IIV of CL and V4 set to 1. Expansion factor of V4 is 0.95 (RSE = 24.4%).
Correlation between IIV of KA and tlag set to 1. Expansion factor of tlag is 2.06 (RSE = 27.7%).
Expressed as standard deviation of the logit domain.
Residual variability, expressed as percentage: Full PK profiles: 24.5 (RSE = 9.52%). Isolated measurements of phase 1 studies: 43.8 (RSE = 18.5%). Isolated measurements of phase 2/3 studies: 72.3 (RSE = 11.3%).
D1 for solid formulation. 0.418 h for liquid formulation. Ratio liquid : solid 0.348 (RSE = 6.01%).
KA for solid formulation. 01.46 h−1for liquid formulation. Ratio liquid : solid 2.07 (RSE = 13.5%).
tlag for solid formulation. 0.019 h (Subpopulation 1) and 0.044 (Subpopulation 2) for liquid formulation. Ratio liquid : solid 0.183 (RSE = 25.8%). IIV = interindividual variability, IOV = interoccasion variability.