Table 2.
Model parameter estimates for the final ritonavir (left column) and joint ritonavir-atazanavir (right column) PK-PG model using a gold standard analysis. Relative standard errors, obtained by nonparametric bootstrap (n=100) and expressed in percentages, are given in parenthesis.
| Ritonavir | Atazanavir | |
|---|---|---|
| CL/F (L/h) | 10.3 (9) | 16.0** (64) |
| βCYP3A5*1 | - | 1.28 (59) |
| AUC50 of RTV (ng.h/mL) | - | 6,230 (91) |
| Emax | - | 0.98 (3) |
| V/F (L) | 87.9 (11) | 81.1 (6) |
| ka (h−1) | 3.9 (58) | 3.3 (146) |
| MTT (h) | 1.1 (16) | 1.36 (14) |
| NN | 14.4 (95) | 11.5 (29) |
| BSV (CL/F) * | 38.5 (33) | 31 (28) |
| BSV (V/F) * | 37.3 (50) | 31 (33) |
| Correlation (CL/F-V/F) | 0.74 (45) | - |
| BSV (ka) * | 248 (161) | 81 (133) |
| BSV (MTT) * | 49.3 (77) | 44 (39) |
| RV week 4 (%) * | 40.8 (8) | 19.4 (16) |
| RV > week 4 (%) * | 40.8 (8) | 42.3 (10) |
*
BSV=Between-subject variability, RV=Residual variability,
**
(CL/F)0=atazanavir CL in absence of ritonavir, MTT=mean transit time, NN=number of transit compartments, ka=absorption rate constant, AUC50 – ritonavir exposure needed for half maximal boosting effect, Emax – maximal effect of ritonavir boosting, βCYP3A5*1 – factor of increase in atazanavir CL with at least one copy of CYP3A5*1 allele, RV=residual variability