TABLE 5

Predicted net DDI vs. that observed and associated geometric fold error assuming total plasma concentrations and interaction in the liver only ( eq. 9 ) or interaction in the liver plus intestine ( eq. 16 ), using all in vitro data (reversible inhibition, time-dependent inactivation, and induction)


Precipitant

Range of DDI (Observed)

[I]H

AUC′/AUC (Predicted) ([I]H)

GFE

[I]G

AUC′/AUC (Predicted) ([I]H + [I]G)

GFE
μM μM
Avasimibe 0.27 0.50 0.63 2.3 12.1 1.4 5.4
Avasimibe 0.06 1.5 0.60 10 181 2.0 33
Azithromycin 0.87–1.3 0.27 1.2 1.1 80.8 2.1 1.9
Azithromycin 1.0 0.27 1.2 1.2 40.4 1.6 1.6
Bosentan 0.66 2.6 0.09 7.4 25.3 0.12 5.5
Carbamazepine 0.26 34 0.09 2.8 154 0.07 3.9
Cimetidine 1–2.2 3.3 1.1 1.4 144 1.7 1.1
Clarithromycin 3.6 2.4 7.8 2.2 40.4 14 3.8
Clarithromycin 5.5–8.4 3.0 8.6 1.2 80.9 15 2.1
Clarithromycin 5.3 2.2 7.5 1.4 80.9 10 1.9
Clarithromycin 10 4.8 10 1.0 80.9 15 1.5
Cyclosporine 8.0 1.9 8.2 1.0 26.8 12 1.6
Cyclosporine 2.6 0.58 4.5 1.8 23.8 6.8 2.7
Diltiazem 3.8 0.14 6.2 1.6 17.5 11 2.9
Diltiazem 3.0 0.14 6.2 2.1 17.5 8.0 2.7
Diltiazem 4.8 0.27 8.4 1.7 35.0 13 2.6
Diltiazem 2.3–3.4 0.14 6.2 2.2 17.5 8.3 3.0
Erythromycin 3.3 0.44 3.0 1.1 33.0 5.3 1.6
Erythromycin 3.8–4.4 0.95 4.7 1.2 82.4 8.3 2.0
Erythromycin 3.8 0.95 4.7 1.2 82.4 6.3 1.7
Erythromycin 6.2 0.95 4.7 1.3 82.4 7.2 1.2
Erythromycin 2.1 3.3 8.6 4.1 54.9 11 5.5
Ethinyl estradiol 1.1–1.2 0.01 1.0 1.1 20.4 1.7 1.5
Fluconazole 3.6 7.2 1.9 1.9 59.3 3.1 1.2
Fluconazole 3.6–4.9 29 4.1 1.1 158 7 1.6
Fluconazole 2.7 22 3.5 1.3 79.1 4.3 1.6
Fluconazole 2.1–4.4 7.2 1.9 1.7 39.5 2.4 1.3
Fluoxetine 0.87 0.36 2.5 2.8 21.0 5.4 6.2
Fluoxetine 1.0 0.36 2.5 2.5 21.0 4.1 4.1
Itraconazole 6.2–10.8 0.27 9.7 1.2 34.3 17 2.2
Itraconazole 10 0.27 9.7 1.0 34.3 15 1.5
Itraconazole 3.1–4.5 0.27 9.7 2.5 34.3 13 3.3
Ketoconazole 14 5.4 14 1.0 45.6 24 1.8
Ketoconazole 5.2–8.7 1.9 13 1.9 45.6 23 3.4
Ketoconazole 9.5–15.9 2.8 14 1.1 91.1 20 1.6
Ketoconazole 9.2–22.4 5.4 14 1.1 45.6 19 1.2
Mibefradil 8.9 1.2 14 1.5 24.4 24 2.7
Mibefradil 8.4 1.2 14 1.6 12.2 19 2.2
Modafinil 0.42 49 0.19 2.2 133 0.26 1.6
Nafcillin 0.37 44 0.24 1.5 133 0.37 1.0
Nelfinavir 6.1 7.1 12 2.0 246 20 3.3
Nifedipine 1.0 0.29 0.71 1.5 21.0 0.42 2.5
Phenobarbital 0.39 52 0.10 3.9 52.1 0.13 3.0
Phenytoin 0.06 70 0.11 1.8 71.9 0.10 1.6
Pioglitazone 0.98 2.8 2.2 2.2 13.9 5.4 5.5
Pleconaril 0.65 2.4 0.17 3.9 122 0.05 12
Raloxifene 1.0 0.001 1.0 1.0 16.1 1.8 1.8
Rifampin 0.016–0.041 12 0.09 3.3 88.2 0.08 2.8
Rifampin 0.08 12 0.09 1.1 88.2 0.11 1.4
Rifampin 0.09–0.14 12 0.09 1.3 88.2 0.09 1.3
Rifampin 0.05 12 0.09 1.8 88.2 0.11 2.1
Ritonavir 20.4–40.7 12 14 1.9 33.6 19 1.4
Rosiglitazone 0.88 0.34 1.8 2.0 2.04 2.6 2.9
Roxithromycin 1.5 5.1 4.5 3.1 43.4 8 5.3
Saquinavir 5.2 0.43 12 2.3 216 23 4.4
Troglitazone 0.62 4.8 13 21 110 21 34
Troleandomycin 3.8 0.15 2.0 1.9 149 4.7 1.3
Verapamil 2.9 0.22 3.3 1.2 21.3 10 3.5
Verapamil 4.7 0.22 3.3 1.4 21.3 9 1.9
   Geometric mean fold error



1.8


2.5
  • Values highlighted in bold are above 2-fold