TABLE 4

Testing R_Met using compounds with clinical drug-drug interaction data

			Parent			Metabolite					Requires Further Analysis for DDI^{^a}
	Clinical DDI^{^b}	Cytochrome P450	I	K_i	I/K_i	I	K_i	I/K_i	Parent K_i/4	R_Met	Parent I/K_i	Metabolite I/K_i	R_Met	Overall^{^c}
			µM	µM		µM	µM		µM
P^{^d}
Fluoxetine	7.8	2D6	0.37	0.2	1.85	0.38	0.2	1.9	0.05	7.6	Y	Y	Y	Y
Itraconazole	36.4	3A4	0.94	8.5	0.11	1.09	26	0.04	2.13	0.51	Y	N	Y	Y
Sulfinpyrazone	1.9	2C9	51	229	0.22	36	27	1.33	57.3	0.63	Y	Y	Y	Y
Omeprazole	1.5	2C19	1.6	2	0.8	0.38	8.2	0.05	0.5	0.76	Y	N	Y	Y
Quinidine M1	42.6	2D6	1.9	0.3	6.33	0.3	2.3	0.13	0.075	4	Y	Y	Y	Y
Quinidine M2	42.6	2D6	1.9	0.3	6.33	0.6	43.5	0.01	0.075	8	Y	N	Y	Y
M^{^d}
Amiodarone	2.1	2C9	1.09	39	0.03	1.16	5.9	0.2	9.8	0.12	N	Y	Y	Y
Bupropion M1	5.2	2D6	0.67	21	0.03	2.34	5.4	0.43	5.25	0.36	N	Y	Y	Y
Bupropion M2	5.2	2D6	0.67	21	0.03	4.01	13	0.3	5.25	0.61	N	Y	Y	Y
Bupropion M3	5.2	2D6	0.67	21	0.03	0.43	1.7	0.25	5.25	0.08	N	Y	N	Y
Gemfibrozil	8	2C8	100	60	1.67	20	12	1.67	15	1.33	Y	Y	Y	Y
Sertraline	1.4	3A4	0.33	3.5	0.09	0.53	3.5	0.15	0.875	0.61	N	Y	Y	Y
U^{^d}
Omeprazole	1.3	3A4	1.6	201	0.01	0.38	188	0	50.3	0.01	N	N	N	N
Ranolazine	1.9	3A4	2.2	90	0.02	0.89	104	0.01	22.5	0.04	N	N	N	N
Sertraline	1.7	2D6	0.25	23	0.01	0.32	16	0.02	5.75	0.06	N	N	N	N
Venlafaxine	1.3	2D6	0.23	30	0.01	0.03	20	0	7.5	0	N	N	N	N
Pfizer clinical compounds
PF-01	1.35	2D6	0.51	35	0.015	0.98	>50	<0.01	8.8	0.11	N	N	Y	Y
PF-03	<1.2	3A4	0.01	4	0.0018	0.08	>85	<0.00094	1.0	0.08	N	N	N	N
PF-06	<1.2	3A4	0.14	9.5	0.015	0.14	>30	<0.0047	2.4	0.059	N	N	N	N
PF-07	2.2	2D6	0.11	0.09	1.2	2.2	>30	<0.08	0.023	98	Y	N	Y	Y
PF-08	1.4	3A4	0.87	0.39	2.2	41.8	>30	<1.4	0.098	429	Y	N	Y	Y

R_Met, = metabolite I/(parent K_i × 0.25); P, parent-mediated DDI; M, metabolite-mediated DDI; U, unexplained DDI; N, no; Y, yes.
↵^a If parent or metabolite I/K_i or R_Met is >0.1, then listed as Y; if <0.1, then listed as N.
↵^b Clinical DDI, reported AUC_I/AUC of victim drug in clinical DDI study.
↵^c If parent or metabolite I/K_i or R_Met is Y, then overall is Y.
↵^d Data on literature cytochrome P450 inhibitors from The University of Washington Metabolism and Transport Drug Interaction Database