TABLE 2

Kinetic parameters of CYP3A TDI (k_inact and K_I), risk factor ratio (k_inact/K_I), initial inactivation rate at 10 μM (k_obs), IC₅₀, and shifted IC₅₀ for 63 drugs estimated after 10-fold dilution of the preincubate with 10 μM midazolam

Drug	k_inact	S.E.	K_I	S.E.	k_inact/K_I	k_obs	IC₅₀	Shifted IC₅₀
	min⁻¹		μM		ml/min · μmol	min⁻¹	μM
Acetaminophen	0.009	0.001	1.5	0.4	5.7	0.007	>5	>5
Amlodipine	0.039	0.001	3.3	0.5	11.5	0.026	>5	0.83
Amprenavir^{^a}	0.174	0.017	1.9	0.3	93.5	0.135	0.26	0.05
Azamulin^{^a}	>0.1		<0.5			0.106	0.07	<0.025
Cilostamide	0.029	0.006	6.0	3.1	4.8	0.014	2.94	1.81
Cilostazol	0.049	0.012	21.9	8.9	2.2	0.010	>5	2.40
Clarithromycin	0.058	0.006	13.2	3.2	4.4	0.026	>5	1.14
Clemizole	0.197	0.026	49.7	8.8	4.0	0.031	>5	0.65
Clozapine	0.014	0.002	5.7	2.3	2.4	0.006	>5	>5
Cyclosporine	0.033	0.003	3.3	0.8	9.9	0.019	>5	1.48
Delavirdine	0.290	0.068	15.9	5.9	18.3	0.112	2.45	0.27
Diltiazem	0.031	0.002	3.6	0.8	8.4	0.022	>5	2.45
Diltiazem-N-desmethyl^{^a}	0.043	0.005	0.8	0.2	51.5	0.032	>0.5	0.19
Dipyridamole	0.039	0.003	5.3	1.0	7.2	0.026	0.89	0.65
Domperidone	0.018	0.002	4.7	1.2	3.9	0.011	>5	>5
Erythromycin	0.041	0.002	26.5	2.4	1.5	0.008	>5	2.30
Estradiol valerate	0.030	0.006	14.9	5.3	2.0	0.007	>5	8.02
Ethinylestradiol	0.254	0.087	58.6	23.7	4.3	0.030	>5	0.94
Fipexide	0.059	0.006	7.2	1.1	8.2	0.036	0.41	0.39
Gestodene	0.107	0.012	15.4	2.7	6.9	0.033	>5	0.62
Hydrastine	0.130	0.016	20.2	4.2	6.4	0.037	>5	0.63
Isradipine	>0.1		>50			0.004	2.74	2.02
Itraconazole^{^a}	0.036	0.014	2.7	6.2	13.0	0.017	<0.25	<0.25
Khellin	>0.1		>50			0.030	>5	0.99
Lansoprazole	0.073	0.055	31.8	32.2	2.3	0.012	>5	1.72
Losartan	0.006	0.001	3.3	1.3	1.8	0.003	>5	<0.25
Mianserin^{^b}	0.093	0.003	3.8	0.3	24.8	0.070	0.98	0.12
Mibefradil^{^a}	>0.1		<0.5			0.046	0.16	<0.025
Mifepristone	0.110	0.004	3.6	0.5	30.6	0.078	1.08	<0.25
Montelukast	0.011	0.003	4.9	4.1	2.2	0.002	>5	7.24
Motesanib	0.038	0.003	7.8	1.4	4.8	0.020	0.61	0.47
Naftidrofuryl^{^b}	0.056	0.002	2.4	0.2	23.2	0.045	>1.2	0.27
Nefazodone^{^b}	0.094	0.010	1.0	0.3	96.5	0.066	0.28	0.07
Nelfinavir^{^b}	0.184	0.048	8.8	3.2	20.9	0.092	0.24	0.12
Nicardipine^{^a}	>0.1		<0.5			0.066	0.07	<0.025
Nimesulide	0.014	0.018	25.4	33.4	0.6	0.005	>5	>5
Nimodipine	0.092	0.015	31.3	7.4	2.9	0.022	0.92	0.75
Omeprazole	0.099	0.025	21.7	7.1	4.6	0.021	>5	1.24
Ondansetron^{^b}	0.048	0.001	0.8	0.2	59.0	0.044	1.04	0.08
Oxatomide	0.039	0.001	4.8	0.9	8.2	0.024	>5	1.01
Phenytoin	0.009	0.001	4.7	1.3	1.9	0.004	>5	>6
Pioglitazone	0.013	0.003	13.0	4.3	1.0	0.004	>5	>5
Pirenzepine^{^b}	0.080	0.003	4.0	0.2	19.8	0.057	>1.2	0.16
Progesterone	0.012	0.003	9.9	4.3	1.2	0.002	2.72	6.02
Propoxyphene	0.034	0.006	15.1	6.7	2.2	0.007	>5	<0.25
Raloxifene	0.163	0.016	4.3	0.8	37.6	0.100	1.32	0.11
Resveratrol	0.120	0.021	46.0	13.1	2.6	0.017	>5	0.87
Risperidone	0.005	0.001	2.9	0.9	1.8	0.003	>5	>5
Ritonavir	>0.1		<0.5				<0.25	<0.25
Rosiglitazone	0.011	0.001	4.4	1.6	2.5	0.006	>5	>5
Ruboxistaurin	0.100	0.006	2.3	0.4	43.5	0.087	2.93	<0.25
Saquinavir^{^b}	0.026	0.007	5.9	2.2	4.4	0.019	0.28	0.32
Simvastatin	0.006	0.003	4.6	2.4	1.4	0.003	2.28	>5
SKF-525A	0.097	0.004	1.0	0.3	101	0.084	>5	<0.25
Sorafenib	0.045	0.001	2.4	0.3	18.9	0.037	>5	0.21
Tadalafil	0.228	0.018	27.5	2.8	8.3	0.058	>5	0.40
Terbinafine	0.009	0.003	10.8	4.8	0.8	0.003	>5	>5
Ticlopidine	0.008	0.001	3.5	2.2	2.3	0.002	>5	>5
Tofisopam	0.210	0.009	6.2	0.4	33.9	0.117	0.92	<0.25
Troglitazone	0.087	0.005	10.0	1.4	8.7	0.040	>5	0.51
Troleandomycin^{^b}	0.141	0.006	0.6	0.1	254	0.129	>1.2	<0.05
Verapamil^{^b}	0.070	0.004	2.4	0.3	29.2	0.060	>1	0.22
Zafirlukast	0.208	0.081	32.3	15.5	6.4	0.042	2.88	0.52

SKF-525A, proadifen hydrochloride.
↵a Tested range 0.25 to 5 μM.
↵b Tested range 0.5 to 12 μM.