Victim Drug | f2D6 | PX | [PX] | Predicted FDCL2D6 Microsomal binding considered? | Predicted FDCLtot Microsomal binding considered? | Predicted AUC Ratio Microsomal binding considered? | Actual AUC Ratio | Percentage Accuracy Microsomal binding considered? | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No | Yes | No | Yes | No | Yes | No | Yes | |||||||||
mg/day | nM | |||||||||||||||
Atomoxetine | 0.90 | 20 | 4.6a | 0.413 | 0.915 | 0.374 | 0.827 | 1.6 | 5.8 | 7.1 | 23 | 82 | ||||
Desipramine | 0.85 | 20 | 5.0a | 0.437 | 0.922 | 0.373 | 0.786 | 1.6 | 4.7 | 5.2 | 31 | 90 | ||||
30 | 8.1a | 0.554 | 0.949 | 0.473 | 0.810 | 1.9 | 5.3 | 5.5 | 35 | 96 | ||||||
20 | 4.0a | 0.383 | 0.904 | 0.327 | 0.771 | 1.5 | 4.4 | 4.6 | 33 | 96 | ||||||
(R)-Metoprolol | 0.89 | 20 | 5.9b | 0.478 | 0.933 | 0.427 | 0.833 | 1.7 | 6.0 | 7.9 | 22 | 76 | ||||
(S)-Metoprolol | 0.80 | 20 | 5.9b | 0.478 | 0.933 | 0.383 | 0.748 | 1.6 | 4.0 | 5.1 | 31 | 78 | ||||
Perphenazine | 0.87 | 20 | 5.9b | 0.478 | 0.933 | 0.416 | 0.811 | 1.7 | 5.3 | >7.0c | N.C.c | N.C. | ||||
Risperidone | 0.89 | 20 | 5.9b | 0.478 | 0.933 | 0.423 | 0.825 | 1.7 | 5.7 | 5.5 | 31 | 104 |
↵ a Paroxetine steady-state plasma unbound concentration from the exposure measured in this study
↵ b Paroxetine steady-state plasma unbound concentration following 20 mg q.d. dosing (Kaye et al., 1989)
↵ c The 7-fold increase is a lower bound, since half-life was prolonged but only AUC0-8 h was measured; predicted accuracy is thus not calculated (N.C.) for the perphenazine-paroxetine interaction