TABLE 2

IC₅₀ values for the inhibition of recombinant UGT2B10 by UGT enzyme-selective inhibitors, azoles, and antidepressant and antipsychotic drugs

Classification	Drug	IC₅₀ (μM) ± S.E. of Parameter Fit^a
UGT enzyme-selective inhibitors
	Desloratadine	3.86 ± 0.05
	Fluconazole	1136 ± 88.4
	Hecogenin	NI
	(-)-Nicotine	214 ± 2.86
	Niflumic acid	168 ± 0.14
	Phenylbutazone	220 ± 35.4
	Loratadine (desloratadine precursor)	2.18 ± 0.34
Azoles
	Itraconazole	NI
	Ketoconazole	11.9 ± 1.69
Antidepressants
TCAs
Primary amine^b	Desmethylnortriptyline	43.7 ± 2.03
	Didesmethylimipramine	36.2 ± 0.40
Secondary amine	Desipramine	34.1 ± 1.04
	Norclomipramine	50.8 ± 4.88
	Nortriptyline	45.3 ± 0.02
	Protriptyline	34.3 ± 0.40
Tertiary amine	Amitriptyline	6.45 ± 0.46
	Clomipramine	26.0 ± 0.49
	Doxepin	3.64 ± 0.16
	Imipramine	42.8 ± 1.52
	Trimipramine	32.6 ± 1.70
Tetracyclic antidepressants
Tertiary amine	Mianserin	2.24 ± 0.11
	Mirtazapine	31.0 ± 0.99
SSRIs
Primary amine	Fluvoxamine	224 ± 6.11
Secondary amine	Fluoxetine	72.4 ± 15.8
	Paroxetine	63.5 ± 4.79
	Sertraline	92.7 ± 8.99
Tertiary amine	Citalopram	218 ± 17.4
SNRIs
Secondary amine	Duloxetine	81.2 ± 8.17
Tertiary amine	Desvenlafaxine	440 ± 16.5
	Venlafaxine	NI
MAOIs
Primary amine	Tranylcypromine	NI
Tertiary amine	Selegiline	67.2 ± 3.60
Hydrazine	Phenelzine	94.2 ± 1.79
Antipsychotics
Typical antipsychotics
Tertiary amine	Chlorpromazine	79.0 ± 10.7
	Fluphenazine	53.5 ± 6.54
	Haloperidol	NI
	Loxapine	36.0 ± 1.82
	Perphenazine	66.2 ± 0.6
	Thioridazine	71.3 ± 18.2
Atypical antipsychotics
Tertiary amine	Aripiprazole	55.8 ± 0.80
	Clozapine	61.3 ± 1.40
	Olanzapine	276 ± 4.49
	Quetiapine	43.9 ± 7.65

NI, negligible inhibition over the concentration range investigated.
↵^a IC₅₀ values were calculated by fitting eq. 5 to experimental data using Enzfitter (see Materials and Methods). Each IC₅₀ value was derived from duplicate measurements at each of four inhibitor concentrations with cotinine as the substrate (see Materials and Methods). S.E. is the standard error of the parameter fit from Enzfitter.
↵^b The designation of primary, secondary, or tertiary amine or hydrazine refers to the N-containing functional group present in the side chain (aliphatic or alicyclic) attached to the mono-, bi-, tri-, or tetracyclic structure (Supplemental Fig. 1).