TABLE 4

Predicted and observed AUC changes of NGMN determined retrospectively from clinical trials

The perpetrator in vitro values shown in Table 3 were used for the DDI predictions. Equations 2–4, as defined in Materials and Methods, were used to calculate the fold changes in the AUC. LPR and RTV were coadministered in one study (Vogler et al., 2010), while ATV and RTV were coadministered in another study (Zhang et al., 2011). Hence, the fold AUC changes are the same for LPR and RTV (study 1) and ATV and RTV (study 2). EFZ was dosed in a separate study (Sevinsky et al., 2011).

PerpetratorNGMNPredicted/Observed Ratio
Concentration ParadigmDoseConcentrationPredicted AUCi/AUCObserved AUCi/AUC
mgnM
Total CmaxLPR (400)14,7902.31.821.28
Free CmaxLPR (400)1182.21.821.24
IhLPR (400)42,5262.31.821.28
Total CmaxRTV study 1 (100)7452.31.821.28
Free CmaxRTV study 1 (100)22.11.821.17
IhRTV study 1 (100)92492.31.821.28
Total CmaxATV (300)96162.31.831.27
Free CmaxATV (300)12982.31.831.26
IhATV (300)29,6672.31.831.27
Total CmaxRTV study 2 (100)20532.31.831.27
Free CmaxRTV study 2 (100)62.31.831.27
IhRTV study 2 (100)92532.31.831.27
Total CmaxEFZ (600)21,1610.40.360.98
Free CmaxEFZ (600)1270.90.362.49
IhEFZ (600)126,8420.70.361.94