Table 3.
Final parameter estimates from the final model and the parameter estimates from 200 bootstrap replicates with their relative standard error (RSE %) and the expected RSE from the design
| Parameter | Final model, mean (RSE %) | 200 bootstrap replicates, mean (RSE %) | Design expected RSE (%) |
|---|---|---|---|
| Pharmacokinetic parameters | |||
| Clp (l h−1) | 31.5 (14.0) | 29.3 (15.7) | 8.6 |
| Vc (l) | 56.7 (33.9) | 50.8 (37.2) | 16.4 |
| ka cap (h−1) | 0.032 (46.7) | 0.026 (34.8) | 8.4 |
| ka sol (h−1) | 0.125 (44.2) | 0.111 (29.4) | |
| Frel | 0.817 (23.5) | 0.88 (19.2) | |
| Q | 71.3 (35.3) | 68.0 (16.6) | |
| Vper | 2090 (35.0) | 2245 (38.0) | |
| CLm (l h−1) | 18.3 (12.9) | 17.2 (14.4) | 10.7 |
| Vm (l) | 2.67 (49.8) | 2.3 (51.9) | 10.7 |
| tlag (min) | 19.3 (1.68) | 19.3 (2.2) | |
| Between-subject variability (%) | |||
| BSV Clp | 22.1 (75.2) | 21.9 (73.3) | 40.0 |
| BSV Vc | 77.3 (48.5) | 85.8 (53.2) | 82.2 |
| BSV ka cap | 91.9 (33.5) | 87.3 (30.5) | 41.2 |
| BSV ka sol | 106.3 (31.4) | 101.7 (26.3) | |
| BSV Frel | 62.3 (24.7) | 60.7 (22.6) | |
| Residual variability (CV %) | |||
| Proportional error | |||
| Itraconazole (%) | 40.8 (16.6) | 40.3 (15.5) | |
| Hydroxy-itraconazole (%) | 47.9 (12.7) | 46.7 (14.2) | |
Clp, clearance of parent drug (itraconazole); Vc, volume of distribution of the central compartment for itraconazole; ka cap, absorption rate for capsules; ka sol, absorption rate for solution; Frel, relative bioavailability; Q, intercompartment clearance; Vper, volume of distribution of peripheral compartment for itraconazole; CLm, clearance for hydroxy-itraconazole; Vm, volume for hydroxy-itraconazole; tlag, lag-time; BSV, between-subject variability.