TABLE 3

Summary of CYP3A4 DDI predictions based on the different models

Precipitant
Dose of Precipitant
Observed DDI
Predicted DDI
Predicted DDI
Combined Model
Simcyp Steady-State Model
Simcyp Time-Based Model
Upper Percentile
Lower Percentile
mg
Drugs demonstrating only reversible inhibition in vitro
    Atomoxetine 120 1.0 1.4 1.0 1.0 1.0 1.0
    Atorvastatin 25a 1.4 1.0 1.0 1.0 1.0 1.0
    Chlorzoxazone 250 1.7 1.1 1.1 1.0 1.0 1.0
    Cimetidine 400 1.4 1.7 1.2 1.0 1.0 1.0
    Cimetidine 800 1.4 1.7 1.3 1.1 1.1 1.0
    Cimetidine 800 1.5 2.2 1.5 1.2 1.4 1.1
    Cimetidine 1200 2.0 1.5 1.4 1.1 1.1 1.0
    Fluconazole 400a 1.9 7.3 2.5 1.6 2.1 1.2
    Fluconazole 200 3.6 11 9.2 2.9 4.4 2.0
    Flumazenil 1.75a,b 0.97 1.0 1.0 1.0 1.0 1.0
    Fluvoxamine 200 1.7 1.2 1.1 1.0 1.1 1.0
    Gatifloxacin 400a 1.1 1.1 1.0 1.1 1.1 1.0
    Itraconazole 200 11 3.2 8.2 8.0 18 3.3
    Itraconazole 100 5.7 2.5 5.9 4.9 9.5 2.8
    Itraconazole 200 6.6 3.2 8.0 3.1 5.8 1.8
    Itraconazole 200 6.2 3.2 8.6 7.0 17 2.8
    Ketoconazole 400a 5.0 9.2 5.2 3.6 5.6 2.3
    Ketoconazole 200 5.2 16 20 13 24 5.8
    Ketoconazole 400 14 16 12 8.1 17 3.8
    Ketoconazole 200 6.5 16 13 12 22 7.1
    Ketoconazole 200 8.7 16 12 10 23 4.8
    Ketoconazole 400 6.5 16 20 7.2 13 3.9
    Ketoconazole 400 9.5 16 22 8.5 24 3.8
    Ketoconazole 400 16 16 21 21 37 9.2
    Parecoxib 40a,b 1.1 1.0 1.0 0.90 1.0 0.80
    Ranitidine 300 1.2 1.1 1.1 1.1 1.1 1.0
    Ranitidine 300 1.3 1.2 1.1 1.0 1.0 1.0
    Ranitidine 300 1.7 1.1 1.1 1.0 1.0 1.0
Drugs demonstrating reversible inhibition and irreversible inactivation in vitro
    Azithromycin 500 1.3 1.7 1.7 1.3 1.6 1.2
    Clarithromycin 500 3.6 9.0 2.7 4.6 12 2.3
    Clarithromycin 1000 8.4 10 4.1 6.2 13 2.5
    Conivaptan 40 3.5 2.5 1.9 1.8 2.4 1.4
    Conivaptan 80 5.8 3.6 3.1 3.3 6.8 2.1
    Diltiazem 180 3.8 4.9 1.6 3.7 7.8 2.1
    Erythromycin 1500 3.8 4.0 3.3 5.4 14 2.5
    Erythromycin 1500 4.4 4.0 2.5 3.9 9.6 2.0
    Nefazodone 400 5.4 2.4 12 8.7 22 3.0
    Roxithromycin 300 1.5 3.0 22 10 27 3.4
Drugs demonstrating induction in vitro
    Carbamazepine 600-800 0.04 0.04 0.02 0.04 0.13 0.01
    Rifampin 600 0.05 0.01 0.01 0.03 0.08 0.01
Drugs demonstrating reversible inhibition and induction in vitro
    Nitrendipine 20a 0.93 1.00 1.0 1.0 1.0 1.0
    Simvastatin 80 1.1 2.1 1.0 1.0 1.1 1.0
    Terbinafine 250 0.76 0.89 1.0 1.0 1.0 1.0
    Valdecoxib 80 1.1 0.89 1.0 1.0 1.0 1.0
Drugs demonstrating reversible inhibition, irreversible inactivation, and induction in vitro
    Fluoxetine 40 0.87 3.5 3.2 3.8 9.1 2.1
    Mibefradil 100 8.9 8.2 139 14 44 2.5
    Saquinavir 3600 2.5 10 3.7 3.9 8.3 1.6
    Saquinavir 3600a 5.2 18 13 12 38 3.1
    Troleandomycin 1000 15 3.0 15 6.0 10 1.5
    Verapamil
240
2.9
7.5
3.1
7.0
16
3.5

  • ↵ a Denotes cases in which midazolam was administered intravenously.

  • ↵ b Denotes cases in which the precipitant was administered intravenously.