TABLE 5

Prediction of -fold increase in AUC (AUCs, day15/AUCs, day1) for plasma midazolam concentrations after repeated oral administration of FK1706 (60 mg) using a dynamic model developed in this study

Observed AUCs,day15/AUCs,day1 was 2.

Inactivation Rate by FK1706kdeg, gkdeg, hPredicted AUCs, day15/AUCs, day1
Final Model: TDI Intestine and Liver, Direct Intestine InhibitionSensitivity Analysis (Contribution of Each Dimension of the Inhibition)
TDI LiverDirect Intestine InhibitionTDI IntestineTDI Intestine, Direct Intestine InhibitionTDI Intestine and Liver
h−1h−1
In vitro CYP3A4/5 inactivation rate (kinact, vitro and KI, vitro)0.05780.06931.661.081.311.391.541.51
0.02100.004952.811.781.311.491.582.33
In vivo CYP3A4/5 inactivation rate (kvivo)0.05780.06932.101.301.301.581.612.06
0.02100.004952.061.311.301.481.571.94