TABLE 2

Model-predicted magnitudes of drug-drug interactions of paroxetine with CYP2D6 substrates, without and with consideration of nonspecific microsomal binding FDCL_2D6 and FDCL_tot refer to the fractional decrement in oral clearance via the CYP2D6 component of net clearance and the fractional decrement in total oral clearance, respectively; f_2D6 refers to the fractional contribution of CYP2D6 to net apparent oral clearance; and [PX] is the steady-state average plasma unbound concentration of paroxetine (PX).

Victim Drug	f_2D6	PX	[PX]	Predicted FDCL_2D6 Microsomal binding considered?			Predicted FDCL_tot Microsomal binding considered?			Predicted AUC Ratio Microsomal binding considered?			Actual AUC Ratio	Percentage Accuracy Microsomal binding considered?
Victim Drug	f_2D6	PX	[PX]					No	Yes	No	Yes	No	Actual AUC Ratio	Yes	No	Yes
		mg/day	nM
Atomoxetine	0.90	20	4.6^a	0.413	0.915	0.374	0.827	1.6	5.8	7.1	23	82
Desipramine	0.85	20	5.0^a	0.437	0.922	0.373	0.786	1.6	4.7	5.2	31	90
		30	8.1^a	0.554	0.949	0.473	0.810	1.9	5.3	5.5	35	96
		20	4.0^a	0.383	0.904	0.327	0.771	1.5	4.4	4.6	33	96
(R)-Metoprolol	0.89	20	5.9^b	0.478	0.933	0.427	0.833	1.7	6.0	7.9	22	76
(S)-Metoprolol	0.80	20	5.9^b	0.478	0.933	0.383	0.748	1.6	4.0	5.1	31	78
Perphenazine	0.87	20	5.9^b	0.478	0.933	0.416	0.811	1.7	5.3	>7.0^c	N.C.^c	N.C.
Risperidone	0.89	20	5.9^b	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 AUC_{0-8 h} was measured; predicted accuracy is thus not calculated (N.C.) for the perphenazine-paroxetine interaction