TABLE 5

Comparison of the predicted change in CYP3A2 enzyme steady-state concentration (E′ss/Ess) and indinavir exposure (AUCi/AUC) with that observed in vivo in rats using different parameters for the inhibitor concentration (Iu) of 2MI

DoseParameter Used for IuUnbound ConcentrationE′ss/EssAUCi/AUC
PredictedObservedPredictedObserved
nM
2 mg/kgCmax2.32 ± 1.50.93 ± 0.041.07 ± 0.043
Cave0.15 ± 0.061.00 ± 0.0020.795 ± 0.041.00 ± 0.00171.19 ± 0.90
Cterminal0.24 ± 0.120.99 ± 0.0041.01 ± 0.0034
20 mg/kgCmax60.8 ± 8.10.35 ± 0.0292.65 ± 0.20
Cave2.71 ± 0.360.92 ± 0.0100.376 ± 0.0261.08 ± 0.0113.62 ± 0.84
Cterminal1.77 ± 0.390.95 ± 0.0111.12 ± 0.011