TABLE 7

Summary of predictions of drug-drug interactions for CYP2D6

Inhibiting Drug	IC₅₀^a	f_u	Affected Drug	Predicted Magnitude of Drug Interaction							Actual Drug Interaction
Inhibiting Drug	IC₅₀^a	f_u	Affected Drug					[I] = C_sys	[I] = f_u × C_sys	[I] = C_{hep,inlet(est)}	Actual Drug Interaction	[I] = f_u × C_{hep,inlet(est)}
	μM
Cimetidine^b	130	0.79	Desipramine	1.14	1.11	2.29	2.05	1.56
Citalopram	30	0.20	Desipramine	1.02	1.00	1.17	1.04	1.50
Diltiazem	>300	0.22	Metoprolol	1.00	1.00	1.01	1.00	1.33
Diphenhydramine	12	0.22	Metoprolol	1.03	1.01	2.17	1.33	1.61
Disulfiram	12	0.04	Desipramine	1.00	1.00	3.86	1.16	1.32
Fluoxetine^c	0.27	0.05	Desipramine	5.20	1.38	8.14	2.45	10.1
Fluvoxamine	5.2	0.23	Desipramine	1.10	1.02	2.87	1.51	1.14
Ketoconazole	28	0.01	Desipramine	1.20	1.00	1.66	1.01	1.02
Paroxetine^b	0.32	0.05	Desipramine	1.87	1.05	6.06	1.54	5.21
Quinidine	0.058	0.13	Desipramine	8.86	5.26	9.83	8.82	6.70
Ranitidine	>300	0.85	Metoprolol	1.00	1.00	1.03	1.03	1.50
Risperidone	12	0.11	Dextromethorphan	1.01	1.00	1.04	1.00	1.03
Sertraline	1.8	0.02	Desipramine	1.34	1.01	5.84	1.21	1.54
Terbinafine	0.041	0.01	Desipramine	9.69	3.00	9.90	5.35	4.90

↵ a Used a value of IC₅₀ = 1000 μM for those drugs for which the measured value was greater than 300 μM
↵ b Paroxetine and cimetidine are mechanism-based inactivators of CYP2D6
↵ c Does not include the effect of norfluoxetine