TABLE 4

Summary of the CYP3A4 inactivation data and the DDI-predicted values of AUC ratio based on time-dependent inactivation data only (TDI term ineq. 9) vs. observed values The values used for [I] in vivo were estimated total systemic plasma concentration.


Precipitant

DDI (Observed)

ki

kinact

Predicted AUC′PO/AUCPO (TDI)

GFE
μM min–1
Azithromycin 1.1 19 0.005 1.2 1.1
Azithromycin 1.0 19 0.005 1.2 1.2
Clarithromycin 3.6 14 0.028 7.3 2.0
Clarithromycin 7.0 14 0.028 7.9 1.1
Clarithromycin 5.3 14 0.028 7.0 1.3
Clarithromycin 10 14 0.028 9.1 1.1
Cyclosporine 8.0 8.9 0.025 7.6 1.1
Cyclosporine 2.6 8.9 0.025 4.3 1.7
Diltiazem 3.8 3.3 0.070 6.1 1.6
Diltiazem 3.0 3.3 0.070 6.1 2.0
Diltiazem 4.8 3.3 0.070 8.1 1.7
Diltiazem 2.8 3.3 0.070 6.1 2.2
Erythromycin 3.3 13 0.025 3.0 1.1
Erythromycin 4.1 13 0.025 4.5 1.1
Erythromycin 3.8 13 0.025 4.5 1.2
Erythromycin 6.2 13 0.025 4.5 1.4
Erythromycin 2.1 13 0.025 7.9 3.7
Ethinyl estradiol 1.2 18 0.040 1.1 1.1
Fluoxetine 0.9 5.3 0.017 3.5 4.1
Fluoxetine 1.0 5.3 0.017 3.5 3.5
Mibefradil 8.9 2.3 0.400 14 1.6
Mibefradil 8.4 2.3 0.400 14 1.7
Nelfinavir 6.1 4.0 0.260 14 2.3
Pioglitazone 1.0 10 0.011 5.5 5.6
Raloxifene 1.0 9.9 0.160 1.0 1.0
Ritonavir 27 0.04 0.330 14 1.9
Rosiglitazone 0.88 12 0.020 2.4 2.7
Roxithromycin 1.5 72 0.023 4.3 2.9
Saquinavir 5.2 0.35 0.170 14 2.6
Troglitazone 0.62 5.0 0.335 14 22
Troleandomycin 3.8 1.3 0.032 6.4 1.7
Verapamil 2.9 2.9 0.150 10 3.5
Verapamil 4.7 2.9 0.150 10 2.2
   Geometric mean fold error




2.7
  • Values highlighted in bold are above 2-fold