Table 2.
Final parameter estimates of basic and final pharmacokinetic model.
| Basic model Est | RSE (%) | Final modelEst | RSE (%) | P value | |
|---|---|---|---|---|---|
| CL/F (l h-1) | 3.27 | 2.3 | 3.35 | 2.4 | |
| θweight (kg-1)* | 0.0136 | 47.1 | 0.03 | ||
| θhepatitis C* | 0.726 | 10.7 | <0.005 | ||
| θASAT > 1.5 ULN* | 0.868 | 8.2 | 0.049 | ||
| θASAT missing* | 0.812 | 16 | |||
| V/F (l) | 106 | 8.2 | 106 | 8.2 | |
| ka (h-1) | 1.66 | 11.7 | 1.68 | 11.4 | |
| Interindividual variability CL/F (%) | 27.4 | 13.4 | 24.9 | 15.5 | |
| Interoccasion variability CL/F (%) | 20.4 | 12.6 | 20.4 | 12.6 | |
| Interoccasion variability V/F (%) | 37.9 | 32.2 | 38.3 | 32.2 | |
| Interindividual variability ka (%) | 38.2 | 40.1 | 37.8 | 39.7 | |
| Correlation factor interoccasion variability CL/F and V/F | 0.710 | 44.4 | 0.692 | 45.4 | |
| Fraction in population 1 (%) | 89.4 | 4.6 | 89.0 | 4.8 | |
| Additive error population 1 (mg × l-1) | 0.326 | 7.0 | 0.326 | 7.0 | |
| Additive error population 2 (mg × l-1) | 0.993 | 22.3 | 0.996 | 22.5 | |
| Increment proportion (t < 2 h) | 2.68 | 7.8 | 2.68 | 7.8 |
ASAT = aspartate aminotransferase, CL/F = apparent clearance, Est = parameter estimate, ka = absorption rate constant, RSE = relative standard error (as calculated with COVARIANCE option of NONMEM), V/F = volume of distribution; P value estimated with randomization test.
*
CL/F = θCL/FX(1 + θweight [WT-70]) ¥ (θhepatitis C)HCV ¥ (θ1.5xULN)(1-MISS)xASAT ¥ (θASAT missing)MISS, in which WT is weight, HCV is 1 for individuals with chronic hepatitis C infection and 0 for all others, ASAT is 1 for patients with baseline ASAT >1.5 ¥ ULN and 0 for all others, and MISS is 1 for patients with no baseline ASAT value and 0 for all others.