Compound | -Fold of AUC Change | Reference | ||||
---|---|---|---|---|---|---|
Predicteda | Observed | frenal
b
| ||||
MLX | 8.33 | * | Unpublished | |||
Theophylline | 1.13-1.16 | 1.11 | 0.18 | Obach 2005c, d, e | ||
Desipramine | 1.00 | 1.02 | 0.70 | Obach 2005c, d, e | ||
Midazolam | 16.7 | 17.0 | <0.01 | Obach 2005;d Galetin 2006e | ||
Tolbutamide | 1.43 | 1.77 | 0.001 | Obach 2005;d Soars 2003e | ||
Omeprazole | 1.74-2.74 | 1.36-2.05 | <0.01 | U of Washington DDI database;d Soars 2003e | ||
Loratadine | 2.48 | 3.47 | Negligible | U of Washington DDI database;d Galetin 2006e, f | ||
Cyclosporine | 3.45 | 4.39 | <0.01 | U of Washington DDI database;d Galetin 2006e, f | ||
Alprazolam | 2.75-4.91 | 3.98 | 0.20 | U of Washington DDI database;d Galetin 2006e, f |
↵ a Predictions are based on our model assuming 200 mg b.i.d. doses of ketoconazole have plasma Cmax of 10 μM and linear pK.
↵ b Information on renal clearance was from Hardman et al. (2001), except that of desipramine was from Physicians Desk Reference (2001).
↵ c Assume substrates are selective (theophylline, desipramine for CYP1A2 and CYP2D6, respectively).
↵ d References for observed AUC changes.
↵ e References of fm.
↵ f The ketoconazole inhibition to the metabolism routes other than CYP3A4 was not considered because the information was not available.
↵* Within 10% of the predicted value.