TABLE 3.
Population parameter estimates of itraconazole from the final model of single-dose and multidose itraconazole data
| Parametera | Population estimate | %SE |
|---|---|---|
| CL/F (liters/h) | 129 | 4.0 |
| V2/F (liters) | 861 | 3.9 |
| Q/F (liters/h) | 153 | 4.2 |
| V3/F (liters) | 2,340 | 4.0 |
| KTR (h−1) | 2.05 | 2.2 |
| ETASCALE | −0.213 | 31.0 |
| FORMF | 0.729 | 8.6 |
| FEDKTR | −0.583 | 2.1 |
| FEDF | −0.269 | 12.2 |
| DDFss | 3.26 | 4.9 |
| STUDYPOP-CL/F | −0.166 | 11.6 |
| STUDYPOP-KTR | 0.338 | 14.4 |
| DDKSPOR | 0.0065 | 6.2 |
| DDKSUBA | 0.00596 | 6.2 |
| DDmax | 0 FIX | |
| BSV (%CV [% shrinkage]) | ||
| BSV-CL/F | 22.1 (27.4) | 5.4 |
| BSV-V2/F | 30.8 (44.4) | 9.4 |
| BSV-KTR | 44.8 (4.5) | 3.0 |
| FVAR | 56.4 (5.0) | 4.3 |
| RV | ||
| Single-dose studies | ||
| Proportional error-fasted (%CV) | 29.3 | 3.2 |
| Additive error-fasted (ng/ml) | 0.168 | 7.6 |
| Proportional error-fed (%CV) | 39.9 | 3.1 |
| Additive error-fed (ng/ml) | 0.14 | 5.0 |
| Multidose studies | ||
| Proportional error (%CV) | 14.1 | 4.3 |
| Additive error (ng/ml) | 0.267 | 10.5 |
CL/F, apparent clearance; V2/F, apparent central volume of distribution; Q/F, apparent intercompartmental clearance; V3/F, apparent peripheral volume of distribution; KTR, transit compartment rate constant; RV, residual variability; ETASCALE, effect of formulation on bioavailability variability; FORMF, effect of formulation on bioavailability; FEDKTR, effect of fed status on transit compartment rate constant; FEDF, effect of fed status on bioavailability; DDFss, effect of daily dose on bioavailability for multidose studies; STUDYPOP, effect of study population (United Kingdom versus United States) on CL/F or KTR; DDKSPOR and DDKSUBA, rate constants for effective daily dose on CL/F for Sporanox and SUBA-itraconazole, respectively; DDmax, maximum effect of effective daily dose on CL/F; BSV, between-subject variability; CV, coefficient of variation; FVAR, common random effect for bioavailability.