Summary of the prediction of in vivo drug-drug interaction from in vitro data based on competitive or noncompetitive inhibition mechanism9-a
| Inhibitor—Inhibited drug | AUC ratio9-b (Predicted AUC ratio9-c) | Iin,u/Ki9-d | |
|---|---|---|---|
| (1) Successful cases: | (i) Sulfaphenazole—tolbutamide | ×5.3 | 200 |
| (2C9) | (×5.0) | ||
| (ii) Ketoconazole—triazolam | ×8.3 | 15 (α-OH), | |
| (3A4) | (×7.8) | 4 (4-OH) | |
| (2) Successful for the metabolic pathway but unsuccessful for the total: | (iii) Quinidine—sparteine | ×2.9 | 60 |
| (2D6) | (×1.3) | ||
| (iv) Ketoconazole—terfenadine | ×10 | 4 | |
| (3A4) | (×1.3) | ||
| (3) Unsuccessful for the metabolic pathway: | (v) Fluoxetine—imipramine | ×1.9 | 0.07 |
| (2D6) | (×1.0) | ||
| (vi) Ciprofloxacin—caffeine | ×1.6 | 0.15 | |
| (1A2) | (×1.1) | ||
| (vii) Omeprazole—diazepam | ×2.0 | 0.03 | |
| (2C19) | (×1.0) | ||
| (viii) Erythromycin—triazolam | ×2.1 | 0.017 (α-OH), | |
| (3A4) | (×1.0) | 0.005 (4-OH) |
↵9-a Predictions were based on the inhibition of the P450 isozyme which is mainly related to the metabolism of the corresponding drug.
↵9-b Change in AUC induced by the drug-drug interaction (observed value).
↵9-c Change in AUC induced by the drug-drug interaction (predicted value).
↵9-d Index for the extent of the drug-drug interaction. Iin,u was calculated using pharmacokinetic parameters of the drug.